Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
10.0
5.5
Journals
Pharmaceutics
Editor’s Choice
share announcement

Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Order results
Result details
Results per page
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
13 pages, 1449 KB  
Article
Log BB Prediction Models Using TLC and HPLC Retention Values as Protein Affinity Data
by Karolina Wanat, Klaudia Michalak and Elżbieta Brzezińska
Pharmaceutics 2024, 16(12), 1534; https://doi.org/10.3390/pharmaceutics16121534 - 30 Nov 2024
Cited by 1 | Viewed by 1602
Abstract
Background: The penetration of drugs through the blood–brain barrier is one of the key pharmacokinetic aspects of centrally acting active substances and other drugs in terms of the occurrence of side effects on the central nervous system. In our research, several regression models [...] Read more.
Background: The penetration of drugs through the blood–brain barrier is one of the key pharmacokinetic aspects of centrally acting active substances and other drugs in terms of the occurrence of side effects on the central nervous system. In our research, several regression models were constructed in order to observe the connections between the active pharmaceutical ingredients’ properties and their bioavailability in the CNS, presented in the form of the log BB parameter, which refers to the drug concentration on both sides of the blood–brain barrier. Methods: Predictive models were created using the physicochemical properties of drugs, and multiple linear regression and a data mining method, i.e., MARSplines, were used to build them. Retention values from protein-affinity chromatography (TLC and HPLC) were introduced into the analyses. In both experiments, the stationary phases were modified with serum albumin, which enriched the obtained chromatographic data, and were then introduced into the models with good results. Results: The conducted analyses confirm that the variables that influence the log BB include high degree of lipophilicity, ionisation capacity and low capability of forming hydrogen bonds. However, the addition of chromatographic data improved the obtained regression results and increased the robustness of the models against an increased number of cases. The linear regression model with chromatographic parameters explains 85% of the log bb variability, whereas the MARSplines model explains 91%. Conclusions: Based on the obtained results, it can be concluded that the use of chromatographic data can increase the robustness of predictive regression models related to penetration through biological barriers. Full article
(This article belongs to the Special Issue Transport of Drugs through Biological Barriers—an Asset or Risk)
►▼ Show Figures

Figure 1

27 pages, 2611 KB  
Review
A Comprehensive Review of the Latest Trends in Spray Freeze Drying and Comparative Insights with Conventional Technologies
by Maria Ioannou Sartzi, Dimitrios Drettas, Marina Stramarkou and Magdalini Krokida
Pharmaceutics 2024, 16(12), 1533; https://doi.org/10.3390/pharmaceutics16121533 - 29 Nov 2024
Cited by 9 | Viewed by 6882
Abstract
Spray freeze drying (SFD) represents an emerging drying technique designed to produce a wide range of pharmaceuticals, foods, and active components with high quality and enhanced stability due to their unique structural characteristics. This method combines the advantages of the well-established techniques of [...] Read more.
Spray freeze drying (SFD) represents an emerging drying technique designed to produce a wide range of pharmaceuticals, foods, and active components with high quality and enhanced stability due to their unique structural characteristics. This method combines the advantages of the well-established techniques of freeze drying (FD) and spray drying (SD) while overcoming their challenges related to high process temperatures and durations. This is why SFD has experienced steady growth in recent years regarding not only the research interest, which is reflected by the increasing number of literature articles, but most importantly, the expanded market adoption, particularly in the pharmaceutical sector. Despite its potential, the high initial investment costs and complex operational requirements may hinder its growth. This paper provides a comprehensive review of the SFD technology, highlighting its advantages over conventional drying techniques and presenting its latest applications focused on pharmaceuticals. It also offers a thorough examination of the principles and the various parameters influencing the process for a better understanding and optimization of the process according to the needs of the final product. Finally, the current limitations of SFD are discussed, and future directions for addressing the economic and technical barriers are provided so that SFD can be widely industrialized, unlocking its full potential for diverse applications. Full article
(This article belongs to the Special Issue Spray Drying in the Pharmaceutical and Nutraceutical Field)
►▼ Show Figures

Graphical abstract

18 pages, 3471 KB  
Article
Population Pharmacokinetic and Pharmacodynamic Study of Palbociclib in Children and Young Adults with Recurrent, Progressive, or Refractory Brain Tumors
by John C. Panetta, Nicholas S. Selvo, David Van Mater and Clinton F. Stewart
Pharmaceutics 2024, 16(12), 1528; https://doi.org/10.3390/pharmaceutics16121528 - 28 Nov 2024
Viewed by 1904
Abstract
Background/Objectives: Palbociclib, an oral CDK 4/6 inhibitor, was evaluated in a Pediatric Brain Tumor Consortium (PBTC) phase 1 (NCT02255461; PBTC-042) study to treat children and young adults with recurrent, progressive, or refractory brain tumors. The objectives of this study were to characterize the [...] Read more.
Background/Objectives: Palbociclib, an oral CDK 4/6 inhibitor, was evaluated in a Pediatric Brain Tumor Consortium (PBTC) phase 1 (NCT02255461; PBTC-042) study to treat children and young adults with recurrent, progressive, or refractory brain tumors. The objectives of this study were to characterize the palbociclib population pharmacokinetics in children enrolled on PBTC-042, to conduct a population pharmacodynamic analysis in this patient population, and to perform a simulation study to assess the role of palbociclib exposure on neutropenia and thrombocytopenia. Methods: The palbociclib population pharmacokinetics and pharmacodynamics were characterized in this patient population (n = 34 patients; 4.9–21.6 years old). Population pharmacokinetics were modeled using a one-compartment model with first-order absorption and elimination. Covariate analysis was performed, evaluating demographics, laboratory values, and concomitant medications. A pharmacodynamic model was used to describe the relation between palbociclib plasma exposure and changes in the ANC and platelet counts. Results: The population estimates for the apparent oral volume, apparent oral clearance, and absorption rate constant were 664.5 L/m2, 36.8 L/h/m2, and 0.48 h−1, respectively. The palbociclib apparent oral clearance was decreased in patients with higher AST values (p = 0.0066). The ANC and platelet pharmacodynamic models estimated that the median (5th–95th percentile) time individuals had grade 3 or greater neutropenia was 4 (0, 21) days. Simulations showed that given 75 mg/m2 palbociclib, 49% of the individuals were expected to have grade 3 or greater neutropenia. Conclusions: Palbociclib pharmacokinetics and pharmacodynamics were adequately characterized in this patient population, no unexpected adverse reactions were noted, and the drug was well tolerated. Full article
(This article belongs to the Special Issue Population Pharmacokinetics and Its Clinical Applications)
►▼ Show Figures

Figure 1

14 pages, 2133 KB  
Article
Usefulness of Size-Exclusion Chromatography–Multi-Angle Light Scattering to Assess Particle Composition and Protein Impurities for Quality Control of Therapeutic Exosome Preparations
by Hirotaka Nishimura, Noritaka Hashii, Tomofumi Yamamoto, Yuchen Sun, Takumi Miura, Yoji Sato and Akiko Ishii-Watabe
Pharmaceutics 2024, 16(12), 1526; https://doi.org/10.3390/pharmaceutics16121526 - 27 Nov 2024
Cited by 2 | Viewed by 3049
Abstract
Background: Extracellular vesicles (EVs), including exosomes, are promising pharmaceutical modalities. They are purified from cell culture supernatant; however, the preparation may contain EVs with the desired therapeutic effects and different types of EVs, lipoproteins, and soluble proteins. Evaluating the composition of particulate impurities [...] Read more.
Background: Extracellular vesicles (EVs), including exosomes, are promising pharmaceutical modalities. They are purified from cell culture supernatant; however, the preparation may contain EVs with the desired therapeutic effects and different types of EVs, lipoproteins, and soluble proteins. Evaluating the composition of particulate impurities and the levels of protein impurities in final preparations is critical for quality control. However, few analytical methods can detect these impurities. Methods: We established and evaluated an analytical method using size-exclusion chromatography–multi-angle light scattering (SEC-MALS) for particle and protein impurity analyses of EV samples. Results: In the particle size distribution analysis of EV samples, SEC-MALS showed higher resolution compared with nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). MALS showed comparable accuracy and precision to that of other methods for particle size evaluation using polystyrene standard beads with 60, 100, or 200 nm diameter. Coupling SEC-MALS with UV detection quantitatively evaluated soluble protein impurities. Proteomic analysis on the SEC-MALS-fractionated samples identified different EV and lipoprotein marker proteins in different fractions. Conclusions: SEC-MALS can characterize EV preparations obtained from human adipose-derived mesenchymal stem cells, suggesting that it can evaluate the particle component composition in various EV samples and therapeutic exosome preparations. Full article
(This article belongs to the Collection Advanced Pharmaceutical Science and Technology in Japan)
►▼ Show Figures

Figure 1

26 pages, 6769 KB  
Review
Effect of Lipid Nanoparticle Physico-Chemical Properties and Composition on Their Interaction with the Immune System
by Laura Catenacci, Rachele Rossi, Francesca Sechi, Daniela Buonocore, Milena Sorrenti, Sara Perteghella, Marco Peviani and Maria Cristina Bonferoni
Pharmaceutics 2024, 16(12), 1521; https://doi.org/10.3390/pharmaceutics16121521 - 26 Nov 2024
Cited by 26 | Viewed by 7226
Abstract
Lipid nanoparticles (LNPs) have shown promise as a delivery system for nucleic acid-based therapeutics, including DNA, siRNA, and mRNA vaccines. The immune system plays a critical role in the response to these nanocarriers, with innate immune cells initiating an early response and adaptive [...] Read more.
Lipid nanoparticles (LNPs) have shown promise as a delivery system for nucleic acid-based therapeutics, including DNA, siRNA, and mRNA vaccines. The immune system plays a critical role in the response to these nanocarriers, with innate immune cells initiating an early response and adaptive immune cells mediating a more specific reaction, sometimes leading to potential adverse effects. Recent studies have shown that the innate immune response to LNPs is mediated by Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs), which recognize the lipid components of the nanoparticles. This recognition can trigger the activation of inflammatory pathways and the production of cytokines and chemokines, leading to potential adverse effects such as fever, inflammation, and pain at the injection site. On the other hand, the adaptive immune response to LNPs appears to be primarily directed against the protein encoded by the mRNA cargo, with little evidence of an ongoing adaptive immune response to the components of the LNP itself. Understanding the relationship between LNPs and the immune system is critical for the development of safe and effective nucleic acid-based delivery systems. In fact, targeting the immune system is essential to develop effective vaccines, as well as therapies against cancer or infections. There is a lack of research in the literature that has systematically studied the factors that influence the interaction between LNPs and the immune system and further research is needed to better elucidate the mechanisms underlying the immune response to LNPs. In this review, we discuss LNPs’ composition, physico-chemical properties, such as size, shape, and surface charge, and the protein corona formation which can affect the reactivity of the immune system, thus providing a guide for the research on new formulations that could gain a favorable efficacy/safety profile. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
►▼ Show Figures

Figure 1

17 pages, 3415 KB  
Article
Study on the Scale-Up Possibility of a Combined Wet Grinding Technique Intended for Oral Administration of Meloxicam Nanosuspension
by Csilla Bartos, Anett Motzwickler-Németh, Dávid Kovács, Katalin Burián and Rita Ambrus
Pharmaceutics 2024, 16(12), 1512; https://doi.org/10.3390/pharmaceutics16121512 - 25 Nov 2024
Cited by 4 | Viewed by 1603
Abstract
Background/Objectives: This article reports on the scalability of a combined wet grinding technique applying planetary ball mill and ZrO2 pearls as the grinding medium. After the determination of the parameters in a laboratory scale, the tenfold scale-up method was set. Meloxicam (MEL) [...] Read more.
Background/Objectives: This article reports on the scalability of a combined wet grinding technique applying planetary ball mill and ZrO2 pearls as the grinding medium. After the determination of the parameters in a laboratory scale, the tenfold scale-up method was set. Meloxicam (MEL) was used as a nonsteroidal anti-inflammatory drug (NSAID) intended for per os delivery. During grinding, the PVA solution was used as a dispersion medium. Methods: The influence of the scaling-up on the particle size, morphology, crystallinity, and intra- and interparticulate phenomena has been studied. Formulation investigations of the milled suspensions were carried out. The dissolution test and the cytotoxicity analyses were accomplished. Results: Submicron MEL particle-containing samples were produced in both grinding scales. After the particle size determination was achieved from the suspensions, the wet milled, dried products were studied. The particle size of the dried products fell into the same range for both scales of milling (the maximum particle size was about 580 nm). There was no significant difference in drug crystallinity after the grindings; 70% of MEL remained crystalline in both cases. A remarkable interaction between the components did not develop as a result of milling. The polarity of the products increased, which resulted in a better dissolution, especially in the case of intestinal fluid (~100% in the first 5 min). The products were not found to be toxic. Conclusions: This research demonstrates that the scaling-up of combined wet grinding technique is feasible by adjusting the milling parameters and the adequate amount of excipient. Full article
(This article belongs to the Special Issue Advances in Oral Administration)
►▼ Show Figures

Figure 1

17 pages, 3988 KB  
Article
Effect of Process Parameters on Nano-Microparticle Formation During Supercritical Antisolvent Process Using Mixed Solvent: Application for Enhanced Dissolution and Oral Bioavailability of Telmisartan Through Particle-Size Control Based on Experimental Design
by Eun-Sol Ha, Heejun Park, Ji-Su Jeong, Seon-Kwang Lee, Hui-Taek Kang, In-hwan Baek and Min-Soo Kim
Pharmaceutics 2024, 16(12), 1508; https://doi.org/10.3390/pharmaceutics16121508 - 24 Nov 2024
Cited by 2 | Viewed by 1631
Abstract
Background/Objectives: This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. Methods: A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution [...] Read more.
Background/Objectives: This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. Methods: A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution concentration, temperature, pressure, injection rate of drug solution, and CO₂ flow rate, on particle formation. Solid-state characterizations of the SAS process particles using XRD and FT-IR confirmed their amorphous nature. The effect of particle size on the kinetic solubility, dissolution, and oral bioavailability of telmisartan was also assessed. Results: Using a mixture of dichloromethane and methanol, telmisartan amorphous nano-microparticles with sizes between 200 and 2000 nm were produced. The key parameters, particularly drug solution concentration and temperature, significantly affected the particle size. Interestingly, the ratio of the solvent mixture also had a significant effect on the particle morphology. Further experiments were performed to determine the conditions for preparing telmisartan amorphous nano-microparticles with various sizes by controlling the solvent mixture ratio and the concentration of the drug solution. It was revealed that a reduction in the amorphous particle size enhanced both the kinetic solubility and dissolution rates, leading to a significantly increased in vivo oral bioavailability in rats compared to unprocessed telmisartan. Conclusions: These findings suggest that SAS processing, utilizing adjustments of process parameters, offers an effective strategy for enhancing the bioavailability of poorly soluble drugs by generating amorphous spherical nano-microparticles with optimized particle size. Full article
(This article belongs to the Special Issue Supercritical Techniques for Pharmaceutical Applications)
►▼ Show Figures

Graphical abstract

15 pages, 4451 KB  
Article
Using Poly(amidoamine) PAMAM-βCD Dendrimer for Controlled and Prolonged Delivery of Doxorubicin as Alternative System for Cancer Treatment
by Kendra Sorroza-Martínez, Ignacio González-Sánchez, Raúl Villamil-Ramos, Marco Cerbón, Jorge Antonio Guerrero-Álvarez, Cristina Coronel-Cruz, Ernesto Rivera and Israel González-Méndez
Pharmaceutics 2024, 16(12), 1509; https://doi.org/10.3390/pharmaceutics16121509 - 23 Nov 2024
Cited by 4 | Viewed by 1520
Abstract
Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results [...] Read more.
Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. Methods: The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by 1H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D2O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. Results: The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. Conclusions: The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment. Full article
(This article belongs to the Special Issue Cyclodextrin-Based Gene and Drug Delivery Applications)
►▼ Show Figures

Figure 1

19 pages, 7317 KB  
Article
Development and Characterization of Spray-Dried Combined Levofloxacin–Ambroxol Dry Powder Inhaler Formulation
by Ruwani K. Suraweera, Kirsten M. Spann, Emad L. Izake, Timothy J. Wells, Xiaodong Wang and Nazrul Islam
Pharmaceutics 2024, 16(12), 1506; https://doi.org/10.3390/pharmaceutics16121506 - 22 Nov 2024
Cited by 3 | Viewed by 1943
Abstract
Background: This study explores the development and characterization of spray-dried composite microparticles consisting of levofloxacin (LVX, a broad-spectrum antibiotic), and ambroxol (AMB, a mucolytic agent that has antibacterial and antibiofilm properties), for the intended application of the drug against lower respiratory tract infections [...] Read more.
Background: This study explores the development and characterization of spray-dried composite microparticles consisting of levofloxacin (LVX, a broad-spectrum antibiotic), and ambroxol (AMB, a mucolytic agent that has antibacterial and antibiofilm properties), for the intended application of the drug against lower respiratory tract infections (LRTIs). Methods: A range of LVX to AMB mass ratios (1:1, 1:0.5, and 1:0.25) were prepared, with and without the use of the dispersibility enhancer leucine (LEU), and spray-dried following pre-optimized parameters to achieve the required particle size (1–5 µm) and flow properties. The formulations were characterized by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and a thermogravimetric analysis (TGA). The in vitro aerosolization performance of the new formulation was evaluated with a twin-stage impinger (TSI) at a flow rate of 60 ± 5 L/min. Using a validated RP-HPLC method, LVX and AMB were quantitatively determined. Results: The combined spray-dried LVX, AMB, and LEU particles were spherically shaped with sizes ranging from 1.9 to 2.9 µm, thus complying with the size requirements for effective deep lung deposition. The dispersibility enhancer leucine produced a high yield and enhanced the flow properties and aerosolization characteristics of the spray-dried formulations. The LVX to AMB mass ratios showed a remarkable impact on the aerosolization properties, with the LVX to AMB 1:1 mass ratio demonstrating the best flow and FPFs for both drugs. There must be a balanced ratio of these components for spray drying the composite particles to obtain composite particles of the required size and with the appropriate flow property. The addition of 5% of LEU significantly (p < 0.005) improved the FPF of all the formulations, probably by enhancing the surface hydrophobicity of the composite particles. Conclusions: The spray-dried combined antibiotics formulation has a strong potential for efficient lung delivery intended for the management of LRTIs. Full article
(This article belongs to the Special Issue Development of Spray-Dried Powders for Pulmonary Drug Delivery)
►▼ Show Figures

Figure 1

16 pages, 5113 KB  
Article
Tailoring Mesalazine Nanosuspension Using Chitosan Polyelectrolyte Complexes with Alginate and Alginate/Hydroxypropyl-Methylcellulose Phthalate
by Amélia Aparecida Rocca Pereira, José Vitor Melchiades Aparecida, Maria Eduarda Ramalho, Leonardo Miziara Barboza Ferreira and Maria Palmira Daflon Gremião
Pharmaceutics 2024, 16(12), 1489; https://doi.org/10.3390/pharmaceutics16121489 - 21 Nov 2024
Cited by 2 | Viewed by 1156
Abstract
Background/Objectives: This study evaluated how the relative proportion of chitosan (CS) to the polyanions alginate (ALG) and hydroxypropyl-methylcellulose phthalate (HP) affects the colloidal properties of mesalazine (MSZ) nanosuspensions as a strategy to produce particles with specific characteristics. Methods: Nanosuspensions were prepared [...] Read more.
Background/Objectives: This study evaluated how the relative proportion of chitosan (CS) to the polyanions alginate (ALG) and hydroxypropyl-methylcellulose phthalate (HP) affects the colloidal properties of mesalazine (MSZ) nanosuspensions as a strategy to produce particles with specific characteristics. Methods: Nanosuspensions were prepared using a bottom–up approach based on acid–base reactions and were modified with CS in a binary mixture with ALG or a ternary mixture with ALG and HP. The particle size, polydispersity index (PDI), zeta potential, morphology, and drug association efficiency were analyzed. Results: Higher proportions of CS relative to the polyanions resulted in smaller, less polydisperse particles. The zeta potential inversion was influenced by the relative proportion of CS in the system. These results were consistent over 30 days and pH exerted an influence on the magnitude of the observed effect. The optimized NS modified with binary CS/ALG blends had the following properties at pH 6.0: an average particle size of 324.9 nm, PDI of 0.5, and zeta potential of +40.8 mV; at pH 4.0, it had an average particle size of 310.4 nm, PDI of 0.4, and zeta potential of +43.6 mV. The optimized NS modified with ternary CS/ALG/HP had the following properties at pH 6.0: an average particle size of 316.7 nm, PDI of 0.5, and zeta potential of +33.9 mV; at pH 4.0, it had an average particle size of 363.5 nm, PDI of 0.6, and zeta potential of +33.9 mV. Conclusions: CS-based polyelectrolyte complexes with ALG and ALG/HP offer an approach to modulating the properties of MSZ nanosuspensions, enabling the production of particles with tailored characteristics. Full article
(This article belongs to the Special Issue Chitosan-Based Nanoparticles as Carriers for Drug Delivery and Biomedical Applications)
►▼ Show Figures

Figure 1

15 pages, 1518 KB  
Article
Two in One: Size Characterization and Accelerated Short-Term Physical Stability of Dual-Drug Suspensions with Two Acidic Compounds (Indomethacin and Naproxen)
by Nadina Zulbeari, Signe Malig Hansen and René Holm
Pharmaceutics 2024, 16(12), 1495; https://doi.org/10.3390/pharmaceutics16121495 - 21 Nov 2024
Cited by 2 | Viewed by 1179
Abstract
Background/Objectives: Co-delivering dual-drug systems have proven to be effective in, for example, anticancer therapy or HIV prophylaxis due to a higher target selectivity and therapeutic efficacy from compound synergism. However, various challenges regarding physical stability can arise during the formulation definition when multiple [...] Read more.
Background/Objectives: Co-delivering dual-drug systems have proven to be effective in, for example, anticancer therapy or HIV prophylaxis due to a higher target selectivity and therapeutic efficacy from compound synergism. However, various challenges regarding physical stability can arise during the formulation definition when multiple drug compounds are included in the same formulation. In this work, the focus was on aqueous suspensions, which could be applied as long-acting injectable formulations to release the drug compounds over weeks to months after administration. Methods: It was possible to gain insights into dual-drug nano- and microsuspensions containing two acidic compounds (indomethacin and naproxen) prepared by milling with dual centrifugation. Information regarding the physical stability of individual suspensions was subtracted and compared to dual-drug suspensions when prepared with the same milling conditions and stored at elevated temperatures of 40 °C. Results: Distinct particle size profiles after milling were obtained dependent on the stabilizer used in both individual and dual-drug suspensions. Most notably, the combination of indomethacin and naproxen in one formulation resulted in smaller sizes of drug particles compared to individual suspensions under the presence of some stabilizers. The obtained particle size profiles further indicated that at least one of the model compounds needed to be sufficiently stabilized from a stabilizer to obtain physically stable dual-drug suspensions over 28 days when stored at 40 °C. Similarly, the particle size distribution was dependent on the individual distribution of the suspensions, which showed a monomodal distribution could be achieved for dual-drug suspensions when at least one of the individual suspensions demonstrated a monomodal distribution in the presence of the stabilizer alone. Over a 28-day period, the smallest particle size was obtained in dual-drug suspensions stabilized with a combination of polysorbate 85 and poloxamer 338 compared to dual-drug suspensions stabilized with only a single stabilizer during preparation, indicating tendencies towards stabilization synergism from a combination of stabilizers as well as the model compounds. Conclusion: Overall, the study showed insights into the preparation and physical stability of dual-drug suspensions containing indomethacin and naproxen. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
►▼ Show Figures

Figure 1

17 pages, 2647 KB  
Article
Biopharmaceutical Characterization and Stability of Nabumetone–Cyclodextrins Complexes Prepared by Grinding
by David Klarić, Željka Soldin, Anna Vincze, Rita Szolláth, György Tibor Balogh, Mario Jug and Nives Galić
Pharmaceutics 2024, 16(12), 1493; https://doi.org/10.3390/pharmaceutics16121493 - 21 Nov 2024
Cited by 3 | Viewed by 1588
Abstract
Background: Nabumetone (NAB) is a poorly soluble nonsteroidal anti-inflammatory prodrug (BCS class II drug) whose solubility is significantly improved by complexation with cyclodextrins (CDs). Methods: The solid complexes, in a 1:1 molar ratio, were prepared by mechanochemical activation by grinding, using β-cyclodextrin [...] Read more.
Background: Nabumetone (NAB) is a poorly soluble nonsteroidal anti-inflammatory prodrug (BCS class II drug) whose solubility is significantly improved by complexation with cyclodextrins (CDs). Methods: The solid complexes, in a 1:1 molar ratio, were prepared by mechanochemical activation by grinding, using β-cyclodextrin (β-CD) and its derivatives, hydroxypropyl- and sulfobutylether-β-cyclodextrin (HP-β-CD and SBE-β-CD). The complexation was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier-transformed infrared spectroscopy (ATR–FTIR). Obtained products were further characterized regarding their solubility, in vitro dissolution, permeability and chemical stability. Results: Co-grinding with HP-β-CD and SBE-β-CD yielded products that showed in vitro dissolution profiles in hydrochloric acid medium (pH 1.2) that were substantially different from that of pure NAB, yielding dissolution efficiency enhancements of 34.86 ± 1.64 and 58.30 ± 0.28 times, respectively, for the optimized products. Their in vitro dissolution and gastrointestinal permeability were also studied in a low-volume environment at pH 6.8, corresponding to the intestinal environment. Both β-CD derivatives increased NAB dissolution rate and NAB mass transport across the biomimetic membrane. The effect of β-CD derivatives on NAB chemical stability was studied under the stress conditions by the developed and validated UHPLC–DAD–HRMS method. In acidic conditions, pure and complexed NAB was prone to hydrolytic degradation, yielding one degradation product—pharmacologically inactive NAB metabolite. However, under the oxidative conditions at elevated temperatures, 10 NAB degradation products were identified from co-ground samples. All systems were stable during photo- and long-term stability studies. Conclusions: NAB complexes with HP-β-CD and SBE-β-CD are promising candidates for pharmaceutical product development. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
►▼ Show Figures

Graphical abstract

27 pages, 11207 KB  
Article
Future-Oriented Nanosystems Composed of Polyamidoamine Dendrimer and Biodegradable Polymers as an Anticancer Drug Carrier for Potential Targeted Treatment
by Katarzyna Strzelecka, Adam Kasiński, Tadeusz Biela, Anita Bocho-Janiszewska, Anna Laskowska, Łukasz Szeleszczuk, Maciej Gawlak, Marcin Sobczak and Ewa Oledzka
Pharmaceutics 2024, 16(11), 1482; https://doi.org/10.3390/pharmaceutics16111482 - 20 Nov 2024
Viewed by 1338
Abstract
Background/Objectives: Camptothecin (CPT) is a well-known chemical compound recognized for its significant anticancer properties. However, its clinical application remains limited due to challenges related to CPT’s high hydrophobicity and the instability of its active form. To address these difficulties, our research focused [...] Read more.
Background/Objectives: Camptothecin (CPT) is a well-known chemical compound recognized for its significant anticancer properties. However, its clinical application remains limited due to challenges related to CPT’s high hydrophobicity and the instability of its active form. To address these difficulties, our research focused on the development of four novel nanoparticulate systems intended for either oral or intravenous administration. Methods: These nanosystems were based on a poly(amidoamine) (PAMAM) dendrimer/CPT complex, which had been coated with biodegradable homo- and copolymers, designed with appropriate physicochemical properties and chain microstructures. Results: The resulting nanomaterials, with diameters ranging from 110 to 406 nm and dispersity values between 0.10 and 0.67, exhibited a positive surface charge and were synthesized using biodegradable poly(L-lactide) (PLLA), poly(L-lactide-co-ε-caprolactone) (PLACL), and poly(glycolide-co-ε-caprolactone) (PGACL). Biological assessments, including cell viability and hemolysis tests, indicated that all polymers demonstrated less than 5% hemolysis, confirming their hemocompatibility for potential intravenous use. Furthermore, fibroblasts exposed to these matrices showed concentration-dependent viability. The entrapment efficiency (EE) of CPT reached up to 27%, with drug loading (DL) values as high as 17%. The in vitro drug release studies lasted over 400 h with the use of phosphate buffer solutions at two different pH levels, demonstrating that time-dependent processes allowed for a gradual and controlled release of CPT from the developed nanosystems. The release kinetics of the active compound at pH 7.4 ± 0.05 and 6.5 ± 0.05 followed near-first-order or first-order models, with diffusion and Fickian/non-Fickian transport mechanisms. Importantly, the nanoparticulate systems enabled the stabilization of the pharmacologically active form of CPT, while providing protection against hydrolysis, even in physiological environments. Conclusions: In our opinion, these results underscore the promising future of biodegradable nanosystems as effective drug delivery systems (DDSs) for targeted cancer treatment, offering stability and efficacy over short, medium, and long-term applications. Full article
(This article belongs to the Special Issue Engineering and Characterisation of Novel Nanomedicine Formulations, 2nd Edition)
►▼ Show Figures

Figure 1

19 pages, 6253 KB  
Article
Development and Evaluation of Lactose-Free Single-Unit and Multiple-Unit Preparations of a BCS Class II Drug, Rivaroxaban
by Daniel Zakowiecki, Peter Edinger, Markos Papaioannou, Michael Wagner, Tobias Hess, Jadwiga Paszkowska, Marcela Staniszewska, Daria Myslitska, Michal Smolenski, Justyna Dobosz, Grzegorz Garbacz and Dorota Haznar Garbacz
Pharmaceutics 2024, 16(11), 1485; https://doi.org/10.3390/pharmaceutics16111485 - 20 Nov 2024
Viewed by 4016
Abstract
Background/Objectives: The aim of the present study was to develop lactose-free formulations of rivaroxaban, a novel oral anticoagulant used for the treatment and prevention of blood clotting. As a BCS Class II drug, rivaroxaban is characterized by poor solubility in aqueous media, [...] Read more.
Background/Objectives: The aim of the present study was to develop lactose-free formulations of rivaroxaban, a novel oral anticoagulant used for the treatment and prevention of blood clotting. As a BCS Class II drug, rivaroxaban is characterized by poor solubility in aqueous media, posing a significant formulation challenge. Methods: To address this, phosphate-based excipients were employed to prepare both traditional single-unit dosage forms (tablets) and modern multiple-unit pellet systems (MUPS). These formulations were successfully developed and thoroughly evaluated for their physical properties and performance. Results: The resulting formulations demonstrated very good mechanical strength, including appropriate hardness and friability, alongside strong chemical stability. Their dissolution profiles met the requirements of the compendial monograph for Rivaroxaban Tablets and were comparable to those of the reference product, Xarelto® film-coated tablets. Conclusions: This study shows the potential for producing effective, stable, and patient-friendly medications that meet the needs of contemporary society, where an increasing number of individuals suffer from lactose intolerance or seek vegan-friendly alternatives. Full article
(This article belongs to the Special Issue Novel Applications of Modern Excipients in Advanced Pharmaceutical Products)
►▼ Show Figures

Graphical abstract

15 pages, 4354 KB  
Article
The Acid-Buffered Engineered Gel Promotes In Vitro Cutaneous Healing and Fights Resistant Bacteria in Wounds
by Fatima Abid, Emmeline Virgo, Tahlia Louise Kennewell, Riya Khetan, Hanif Haidari, Zlatko Kopecki, Yunmei Song and Sanjay Garg
Pharmaceutics 2024, 16(11), 1484; https://doi.org/10.3390/pharmaceutics16111484 - 20 Nov 2024
Viewed by 1382
Abstract
Background: Treatment of cutaneous wound infections is becoming a major clinical challenge due to the growing problem of antimicrobial resistance associated with existing wound treatments. Two prevalent pathogens in wound infections, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. [...] Read more.
Background: Treatment of cutaneous wound infections is becoming a major clinical challenge due to the growing problem of antimicrobial resistance associated with existing wound treatments. Two prevalent pathogens in wound infections, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), continue to present a serious challenge, underscoring the critical need for new therapeutic alternatives. Methods: Novel alginate acid-buffered gels (ABF-1, ABF-2, and ABF-3) were developed using a combination of organic acids in various concentrations and buffered at a pH of 4.5. The acid-buffering capacity of the gels was evaluated against sodium hydroxide solution and simulated wound fluid (SWF) at different wound pHs, mimicking infected and non-infected wound environments. The in vitro antibacterial activity was assessed against resistant bacterial strains (Gram-positive and Gram-negative) using a microdilution method and wound biofilm assay. The rheological properties and cell viability of the gels were evaluated and the gel showing positive cell viability was further investigated for healing ability using an in vitro wound scratch assay. Results: The gels showed promising in vitro antibacterial activity against Staphylococcus epidermidis, S. aureus, and P. aeruginosa. Gels with higher acid concentrations (ABF-1 and ABF-2) were highly effective in reducing the bacterial load in chronic biofilms of S. aureus and P. aeruginosa, while the gel with a lower acid concentration (ABF-3) showed positive effects on the viability of skin cells (over 80% cells viable) and for promoting wound closure. All three gels demonstrated excellent acid-buffering capabilities. Conclusions: The acid-buffered gels demonstrate promising in vitro antibacterial effects, indicating their potential for enhancing wound healing. Full article
(This article belongs to the Special Issue Prospects of Hydrogels in Wound Healing)
►▼ Show Figures

Graphical abstract

47 pages, 3373 KB  
Review
The Application of Nano Drug Delivery Systems in Female Upper Genital Tract Disorders
by Daniélle van Staden, Minja Gerber and Hendrik J. R. Lemmer
Pharmaceutics 2024, 16(11), 1475; https://doi.org/10.3390/pharmaceutics16111475 - 19 Nov 2024
Cited by 5 | Viewed by 4133
Abstract
The prevalence of female reproductive system disorders is increasing, especially among women of reproductive age, significantly impacting their quality of life and overall health. Managing these diseases effectively is challenging due to the complex nature of the female reproductive system, characterized by dynamic [...] Read more.
The prevalence of female reproductive system disorders is increasing, especially among women of reproductive age, significantly impacting their quality of life and overall health. Managing these diseases effectively is challenging due to the complex nature of the female reproductive system, characterized by dynamic physiological environments and intricate anatomical structures. Innovative drug delivery approaches are necessary to facilitate the precise regulation and manipulation of biological tissues. Nanotechnology is increasingly considered to manage reproductive system disorders, for example, nanomaterial imaging allows for early detection and enhances diagnostic precision to determine disease severity and progression. Additionally, nano drug delivery systems are gaining attention for their ability to target the reproductive system successfully, thereby increasing therapeutic efficacy and decreasing side effects. This comprehensive review outlines the anatomy of the female upper genital tract by highlighting the complex mucosal barriers and their impact on systemic and local drug delivery. Advances in nano drug delivery are described for their sustainable therapeutic action and increased biocompatibility to highlight the potential of nano drug delivery strategies in managing female upper genital tract disorders. Full article
(This article belongs to the Special Issue Drug Delivery in the Reproductive Systems)
►▼ Show Figures

Graphical abstract

24 pages, 1938 KB  
Article
Orange Peel Lactiplantibacillus plantarum: Development of A Mucoadhesive Nasal Spray with Antimicrobial and Anti-inflammatory Activity
by Elisa Corazza, Asia Pizzi, Carola Parolin, Barbara Giordani, Angela Abruzzo, Federica Bigucci, Teresa Cerchiara, Barbara Luppi and Beatrice Vitali
Pharmaceutics 2024, 16(11), 1470; https://doi.org/10.3390/pharmaceutics16111470 - 18 Nov 2024
Cited by 2 | Viewed by 2091
Abstract
Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum [...] Read more.
Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum BIA was isolated from orange peel and taxonomically identified through 16S rRNA gene sequencing. Its antibacterial activity was tested against Pseudomonas aeruginosa, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, while anti-inflammatory potential was evaluated by Griess assay. BIA genome was fully sequenced and analyzed to assess its safety. BIA was formulated in a freeze-dried matrix, containing prebiotics and cryoprotectants, to be reconstituted with a polymer solution. Solutions containing two types of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid were evaluated as resuspending media and compared in terms of pH, viscosity, and mucoadhesion ability. The biological activity of BIA formulated as nasal spray was verified together with the stability of the selected formulations. Results: L. plantarum BIA inhibited human pathogens’ growth and showed anti-inflammatory activity and a safe profile. In the best-performing formulation, the probiotic is lyophilized in 10% fructooligosaccharides, 0.1% ascorbic acid, and 0.5% lactose and reconstituted with HPMC high viscosity 1% w/v. This composition ensured the probiotic’s viability for up to six months in its dried form and one week after reconstitution. It also allowed interaction with the nasal mucosa, preserving its antimicrobial and anti-inflammatory activities. Conclusion: The developed nasal spray could become a promising formulation in the field of nasal infectious and inflammatory diseases. Full article
(This article belongs to the Special Issue Advances and Challenges in Nasal Formulation Developments, 2nd Edition)
►▼ Show Figures

Graphical abstract

28 pages, 2973 KB  
Review
Peptide-Based Biomaterials for Combatting Infections and Improving Drug Delivery
by Lucia Lombardi, Jiaxu Li and Daryl R. Williams
Pharmaceutics 2024, 16(11), 1468; https://doi.org/10.3390/pharmaceutics16111468 - 18 Nov 2024
Cited by 3 | Viewed by 2900
Abstract
This review explores the potential of peptide-based biomaterials to enhance biomedical applications through self-assembly, biological responsiveness, and selective targeting. Peptides are presented as versatile agents for antimicrobial activity and drug delivery, with recent approaches incorporating antimicrobial peptides into self-assembling systems to improve effectiveness [...] Read more.
This review explores the potential of peptide-based biomaterials to enhance biomedical applications through self-assembly, biological responsiveness, and selective targeting. Peptides are presented as versatile agents for antimicrobial activity and drug delivery, with recent approaches incorporating antimicrobial peptides into self-assembling systems to improve effectiveness and reduce resistance. The review also covers peptide-based nanocarriers for cancer drug delivery, highlighting their improved stability, targeted delivery, and reduced side effects. The focus of this work is on the bioactive properties of peptides, particularly in infection control and drug delivery, rather than on their structural design or material characteristics. Additionally, it examines the role of peptidomimetics in broadening biomaterial applications and enhancing resistance to enzymatic degradation. Finally, the review discusses the commercial prospects and challenges of translating peptide biomaterials into clinical applications. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
►▼ Show Figures

Graphical abstract

18 pages, 4455 KB  
Article
Comprehensive In Vitro and In Silico Aerodynamic Analysis of High-Dose Ibuprofen- and Mannitol-Containing Dry Powder Inhalers for the Treatment of Cystic Fibrosis
by Petra Party, Zsófia Ilona Piszman, Árpád Farkas and Rita Ambrus
Pharmaceutics 2024, 16(11), 1465; https://doi.org/10.3390/pharmaceutics16111465 - 17 Nov 2024
Cited by 6 | Viewed by 2214
Abstract
Background: Cystic fibrosis is a hereditary disease, which causes the accumulation of dense mucus in the lungs accompanied by frequent local inflammation. The non-steroidal anti-inflammatory drug ibuprofen (IBU) and the mucolytic mannitol (MAN) can treat these symptoms. Compared to per os administration, a [...] Read more.
Background: Cystic fibrosis is a hereditary disease, which causes the accumulation of dense mucus in the lungs accompanied by frequent local inflammation. The non-steroidal anti-inflammatory drug ibuprofen (IBU) and the mucolytic mannitol (MAN) can treat these symptoms. Compared to per os administration, a lower dose of these drugs is sufficient to achieve the desired effect by delivering them in a pulmonary manner. However, it is still a challenge to administer high drug doses to the lungs. We aim to develop two inhaled powder formulations, a single-drug product of MAN and a combined formulation containing IBU and MAN. Methods: MAN was dissolved in an aqueous solution of Poloxamer-188 (POL). In the case of the combined formulation, a suspension was first prepared in a planetary mill via wet milling in POL medium. After the addition of leucine (LEU), the formulations were spray-dried. The prepared DPI samples were analyzed by using laser diffraction, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, density tests, in vitro aerodynamic studies (Andersen Cascade Impactor, Spraytec® device), in vitro dissolution tests in artificial lung fluid, and in silico tests with stochastic lung model. Results: The DPIs showed suitability for inhalation with low-density spherical particles of appropriate size. The LEU-containing systems were characterized by high lung deposition and adequate aerodynamic diameter. The amorphization during the procedures resulted in rapid drug release. Conclusions: We have successfully produced a single-drug formulation and an innovative combination formulation, which could provide complex treatment for patients with cystic fibrosis to improve their quality of life. Full article
(This article belongs to the Special Issue Development of Spray-Dried Powders for Pulmonary Drug Delivery)
►▼ Show Figures

Graphical abstract

16 pages, 6646 KB  
Article
Green Synthesis of Zinc Oxide Nanoparticles Using Puerarin: Characterization, Antimicrobial Potential, Angiogenesis, and In Ovo Safety Profile Assessment
by Sergio Liga, Raluca Vodă, Lavinia Lupa, Cristina Paul, Nicoleta Sorina Nemeş, Delia Muntean, Ștefana Avram, Mihaela Gherban and Francisc Péter
Pharmaceutics 2024, 16(11), 1464; https://doi.org/10.3390/pharmaceutics16111464 - 16 Nov 2024
Cited by 1 | Viewed by 2271
Abstract
Background: Zinc oxide nanobiocomposites were successfully synthesized using a green synthesis approach. The process involves the utilization of the isoflavone puerarin, resulting in the formation of PUE-ZnO NPs. Methods: Physico-chemical and biological characterization techniques including X-ray dif-fraction (XRD), UV-vis spectroscopy, Fourier transform infrared [...] Read more.
Background: Zinc oxide nanobiocomposites were successfully synthesized using a green synthesis approach. The process involves the utilization of the isoflavone puerarin, resulting in the formation of PUE-ZnO NPs. Methods: Physico-chemical and biological characterization techniques including X-ray dif-fraction (XRD), UV-vis spectroscopy, Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), and in ovo methods were employed to study the main characteristics of this novel hybrid material. Results: The PUE-ZnO NPs were confirmed to have been successfully synthesized with a UV absorption peak at 340 nm, the XRD analysis demonstrating their high purity and crystallinity. The energy band-gap value of 3.30 eV suggests possible photocatalytic properties. Both SEM and AFM images revealed the nanoparticle`s quasi-spherical shape, roughness, and size. Good tolerability and anti-irritative effects were recorded in ovo on the chorioallantoic membrane (CAM). Conclusions: According to these results, the synthesis of green PUE-ZnO NPs may be a promising future approach for biomedical and personal care applications. Full article
(This article belongs to the Special Issue Advanced Nanotechnology for Combination Therapy and Diagnosis)
►▼ Show Figures

Figure 1

13 pages, 3660 KB  
Article
A Perspective on the Use of Hydroxyapatites to Improve the Dissolution Behavior of Poorly Water-Soluble Piretanide
by Valeria Friuli, Claudia Loi, Giovanna Bruni, Lauretta Maggi and Marcella Bini
Pharmaceutics 2024, 16(11), 1450; https://doi.org/10.3390/pharmaceutics16111450 - 13 Nov 2024
Viewed by 1547
Abstract
Background/Objectives: Interest in drug delivery systems (DDS) based on inorganic substrates has increased in parallel with the increase in the number of poorly water-soluble drugs. Hydroxyapatite is one of the ideal matrices for DDS due to its biocompatibility, low cost, and ease of [...] Read more.
Background/Objectives: Interest in drug delivery systems (DDS) based on inorganic substrates has increased in parallel with the increase in the number of poorly water-soluble drugs. Hydroxyapatite is one of the ideal matrices for DDS due to its biocompatibility, low cost, and ease of preparation. Methods: We propose two doped hydroxyapatites, one with Ba on Ca sites another with Si on P sites, with the aim of improving the dissolution rate of piretanide, a diuretic, poorly water-soluble drug. The hybrids were characterized by different physical–chemical techniques, and their formation was demonstrated by infrared spectroscopy, thermal analysis, and electron microanalysis, as well as by comparing the results with those obtained on physical mixtures of HAPs and properly prepared piretanide. Results: Both the hybrids improved the piretanide dissolution rate compared with the physical mixtures and the drug alone. The dose was completely solubilized from the Si-doped hybrid in about 5 min in the three fluids considered. This remarkable improvement can be explained by an increase in the wettability and solubility of the drug loaded in the drug-carrier systems. Conclusions: Different experimental techniques, in particular spectroscopy and electronic microanalysis, proved the successful loading of piretanide onto doped HAP. Pharmaceutical measurements demonstrated rapid drug release in different fluids simulating gastrointestinal conditions after oral administration. These hybrid systems could be a very promising platform for drug delivery. Full article
(This article belongs to the Special Issue Emerging Technologies to Improve the Solubility of Poorly Soluble Drugs)
►▼ Show Figures

Figure 1

15 pages, 3198 KB  
Article
Inhalable Anti-EGFR Antibody-Conjugated Osimertinib Liposomes for Non-Small Cell Lung Cancer
by Apoorva Daram, Shruti S. Sawant, Dhwani A. Mehta, Carlos A. Sanhueza and Nitesh K. Kunda
Pharmaceutics 2024, 16(11), 1444; https://doi.org/10.3390/pharmaceutics16111444 - 12 Nov 2024
Cited by 5 | Viewed by 2564
Abstract
Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths globally. The most extensive treatment is Tyrosine Kinase Inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) overexpression. Osimertinib, a third-generation TKI is approved to target EGFR exon 19 [...] Read more.
Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths globally. The most extensive treatment is Tyrosine Kinase Inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) overexpression. Osimertinib, a third-generation TKI is approved to target EGFR exon 19 deletions or exon 21 L858R mutations. However, resistance is inevitable due to emergence of triple mutations (sensitizing mutations, T790M and C797S). To overcome this challenge, a combinatorial approach was used wherein Osimertinib liposomes were conjugated with cetuximab (CTX), an anti-EGFR monoclonal antibody, to improve drug efficacy and delivery. Additionally, pulmonary administration was employed to minimize systemic toxicity and achieve high lung concentrations. Methods: Osimertinib liposomes (OB-LPs) were prepared using thin film hydration method and immunoliposomes (CTX-OB-LPs) were prepared by conjugating the OB-LPs surface with CTX. Liposomes were characterized for particle size, zeta-potential, drug loading, antibody conjugation efficiency, in vitro drug release, and aerosolization performance. Further, the in vitro efficacy of immunoliposomes was evaluated in H1975 cell line. Results: Immunoliposomes exhibited a particle size of 150 nm, high antibody conjugation efficiency (87%), efficient drug release, and excellent aerosolization properties with an aerodynamic diameter of 3 μm and fine particle fraction of 88%. Furthermore, in vitro studies in H1975 cells showed enhanced cytotoxicity with CTX-OB-LPs displaying 1.7-fold reduction and 1.2-fold reduction in IC50 compared to Osimertinib and OB-LPs, respectively. The CTX-OB-LPs also significantly reduced tumor cell migration and colonization compared to Osimertinib and OB-LPs. Conclusions: These successful results for EGFR-targeting inhalable immunoliposomes exhibited potential for contributing to greater anti-tumor efficacy for the treatment of non-small cell lung cancer. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
►▼ Show Figures

Figure 1

13 pages, 2081 KB  
Article
FDA and EMA Oversight of Disruptive Science on Application of Finite Absorption Time (F.A.T.) Concept in Oral Drug Absorption: Time for Scientific and Regulatory Changes
by Elias Toulitsis, Athanasios A. Tsekouras and Panos Macheras
Pharmaceutics 2024, 16(11), 1435; https://doi.org/10.3390/pharmaceutics16111435 - 11 Nov 2024
Cited by 1 | Viewed by 1498
Abstract
Background: It has been demonstrated that the concept of infinite absorption time, associated with the absorption rate constant, which drives a drug’s gastrointestinal absorption rate, is not physiologically sound. The recent analysis of oral drug absorption data based on the finite absorption time [...] Read more.
Background: It has been demonstrated that the concept of infinite absorption time, associated with the absorption rate constant, which drives a drug’s gastrointestinal absorption rate, is not physiologically sound. The recent analysis of oral drug absorption data based on the finite absorption time (F.A.T.) concept and the relevant physiologically based finite-time pharmacokinetic (PBFTPK) models developed provided a better physiologically sound description of oral drug absorption. Methods: In this study, we re-analyzed, using PBFTPK models, seven data sets of ketoprofen, amplodipine, theophylline (three formulations), and two formulations (reference, test) from a levonorgestrel bioequivalence study. Equations for one-compartment-model drugs, for the estimation of fraction of dose absorbed or the bioavailable fraction exclusively from oral data, were developed. Results: In all cases, meaningful estimates for (i) the number of absorption stages, namely, one for ketoprofen and the levonorgestrel formulations, two for amlodipine, the immediate-release theophylline formulation, and the extended-release Theotrim formulation, and three for the extended-release Theodur formulation, (ii) the duration of each absorption stage and the corresponding drug input rate, and (iii) the total duration of drug absorption, which ranged from 0.75 h (ketoprofen) to 11.6 h for Theodur were derived. Estimates for the bioavailable fraction of ketoprofen and two theophylline formulations exhibiting one-compartment-model kinetics were derived. Conclusions: This study provides insights into the detailed characteristics of oral drug absorption. The use of PBFTPK models in drug absorption analysis can be leveraged as a computational framework to discontinue the perpetuation of the mathematical fallacy of classical pharmacokinetic analysis based on the absorption rate constant as well as in the physiologically based pharmacokinetic (PBPK) studies and pharmacometrics. The present study is an additional piece of evidence for the scientific and regulatory changes required to be implemented by the regulatory agencies in the not-too-distant future. Full article
(This article belongs to the Special Issue Drug Product Performance: Bioavailability, Relative Bioavailability and Bioequivalence, 2nd Edition)
►▼ Show Figures

Graphical abstract

21 pages, 2940 KB  
Article
Cord Blood Platelet Lysate-Loaded Thermo-Sensitive Hydrogels for Potential Treatment of Chronic Skin Wounds
by Arianna Grivet-Brancot, Marianna Buscemi, Gianluca Ciardelli, Simona Bronco, Susanna Sartori, Claudio Cassino, Tamer Al Kayal, Paola Losi, Giorgio Soldani and Monica Boffito
Pharmaceutics 2024, 16(11), 1438; https://doi.org/10.3390/pharmaceutics16111438 - 11 Nov 2024
Cited by 1 | Viewed by 1428
Abstract
Background/Objectives: Chronic skin wounds (CSWs) are a worldwide healthcare problem with relevant impacts on both patients and healthcare systems. In this context, innovative treatments are needed to improve tissue repair and patient recovery and quality of life. Cord blood platelet lysate (CB-PL) holds [...] Read more.
Background/Objectives: Chronic skin wounds (CSWs) are a worldwide healthcare problem with relevant impacts on both patients and healthcare systems. In this context, innovative treatments are needed to improve tissue repair and patient recovery and quality of life. Cord blood platelet lysate (CB-PL) holds great promise in CSW treatment thanks to its high growth factors and signal molecule content. In this work, thermo-sensitive hydrogels based on an amphiphilic poly(ether urethane) (PEU) were developed as CB-PL carriers for CSW treatment. Methods: A Poloxamer 407®-based PEU was solubilized in aqueous medium (10 and 15% w/v) and added with CB-PL at a final concentration of 20% v/v. Hydrogels were characterized for their gelation potential, rheological properties, and swelling/dissolution behavior in a watery environment. CB-PL release was also tested, and the bioactivity of released CB-PL was evaluated through cell viability, proliferation, and migration assays. Results: PEU aqueous solutions with concentrations in the range 10–15% w/v exhibited quick (within a few minutes) sol-to-gel transition at around 30–37 °C and rheological properties modulated by the PEU concentration. Moreover, CB-PL loading within the gels did not affect the overall gel properties. Stability in aqueous media was dependent on the PEU concentration, and payload release was completed between 7 and 14 days depending on the polymer content. The CB-PL-loaded hydrogels also showed biocompatibility and released CB-PL induced keratinocyte migration and proliferation, with scratch wound recovery similar to the positive control (i.e., CB-PL alone). Conclusions: The developed hydrogels represent promising tools for CSW treatment, with tunable gelation properties and residence time and the ability to encapsulate and deliver active biomolecules with sustained and controlled kinetics. Full article
►▼ Show Figures

Figure 1

29 pages, 5701 KB  
Article
Polysaccharide-Stabilized Semisolid Emulsion with Vegetable Oils for Skin Wound Healing: Impact of Composition on Physicochemical and Biological Properties
by Giovanna Araujo de Morais Trindade, Laiene Antunes Alves, Raul Edison Luna Lazo, Kamila Gabrieli Dallabrida, Jéssica Brandão Reolon, Juliana Sartori Bonini, Karine Campos Nunes, Francielle Pelegrin Garcia, Celso Vataru Nakamura, Fabiane Gomes de Moraes Rego, Roberto Pontarolo, Marcel Henrique Marcondes Sari and Luana Mota Ferreira
Pharmaceutics 2024, 16(11), 1426; https://doi.org/10.3390/pharmaceutics16111426 - 8 Nov 2024
Cited by 5 | Viewed by 1880
Abstract
Background/Objectives: The demand for natural-based formulations in chronic wound care has increased, driven by the need for biocompatible, safe, and effective treatments. Natural polysaccharide-based emulsions enriched with vegetable oils present promising benefits for skin repair, offering structural support and protective barriers suitable for [...] Read more.
Background/Objectives: The demand for natural-based formulations in chronic wound care has increased, driven by the need for biocompatible, safe, and effective treatments. Natural polysaccharide-based emulsions enriched with vegetable oils present promising benefits for skin repair, offering structural support and protective barriers suitable for sensitive wound environments. This study aimed to develop and evaluate semisolid polysaccharide-based emulsions for wound healing, incorporating avocado (Persea gratissima) and blackcurrant (Ribes nigrum) oils (AO and BO, respectively). Both gellan gum (GG) and kappa-carrageenan (KC) were used as stabilizers due to their biocompatibility and gel-forming abilities. Methods: Four formulations were prepared (F1-GG-AO; F2-KC-AO; F3-GG-BO; F4-KC-BO) and evaluated for physicochemical properties, spreadability, rheology, antioxidant activity, occlusive and bioadhesion potential, biocompatibility, and wound healing efficacy using an in vitro scratch assay. Results: The pH values (4.74–5.06) were suitable for skin application, and FTIR confirmed excipient compatibility. The formulations showed reduced occlusive potential, pseudoplastic behavior with thixotropy, and adequate spreadability (7.13–8.47 mm2/g). Lower bioadhesion indicated ease of application and removal, enhancing user comfort. Formulations stabilized with KC exhibited superior antioxidant activity (DPPH scavenging) and fibroblast biocompatibility (CC50% 390–589 µg/mL) and were non-hemolytic. Both F2-KC-AO and F4-KC-BO significantly improved in vitro wound healing by promoting cell migration compared to other formulations. Conclusions: These findings underscore the potential of these emulsions for effective wound treatment, providing a foundation for developing skin care products that harness the therapeutic properties of polysaccharides and plant oils in a natural approach to wound care. Full article
(This article belongs to the Special Issue Dosage Form Design and Delivery Therapy for Skin Disorders)
►▼ Show Figures

Figure 1

21 pages, 1576 KB  
Review
Corneal Treatment, Repair, and Regeneration: Exosomes at Rescue
by Brooke T. Robbins, Kate A. Montreuil, Neloy Kundu, Prashant Kumar and Vibhuti Agrahari
Pharmaceutics 2024, 16(11), 1424; https://doi.org/10.3390/pharmaceutics16111424 - 7 Nov 2024
Cited by 10 | Viewed by 3051
Abstract
Exosomes are extracellular vesicles within the nanosized range that play roles in intercellular communication and thus have certain biological activities. The secretory signaling communication mechanism is an efficient way of exchanging information between cells and has been investigated as nature’s therapeutic drug carriers. [...] Read more.
Exosomes are extracellular vesicles within the nanosized range that play roles in intercellular communication and thus have certain biological activities. The secretory signaling communication mechanism is an efficient way of exchanging information between cells and has been investigated as nature’s therapeutic drug carriers. This review will summarize the potential of exosomes as therapeutic tools and drug delivery vehicles for corneal pathologies. The cornea is an avascular ocular tissue, and its healing is a complex process including cell death and migration, cell proliferation and differentiation, and extracellular matrix remodeling. Here, we discussed the structure, barrier, phases, and healing cascade of cornea. We briefly reviewed the immunogenicity and toxicity of exosomes and role of exosomes in preserving cornea. Additionally, we provided combining exosome strategies with hydrogels, gene and stem cells therapy focused on corneal treatment, repair, and regeneration. Full article
(This article belongs to the Special Issue Emerging Trends and Translational Challenges in Drug and Vaccine Delivery, 2nd Edition)
►▼ Show Figures

Figure 1

19 pages, 9902 KB  
Article
Antiproliferative and Morphological Effects of Fenretinide Lipid Nanosystems in Colon Adenocarcinoma Cells
by Lorenzo Anconelli, Francesca Farioli, Pietro Lodeserto, Aikaterini Andreadi, Francesca Borsetti, Manuela Voltattorni, Lucrezia Galassi, Martina Rossi, Giovanna Farruggia, Paolo Blasi and Isabella Orienti
Pharmaceutics 2024, 16(11), 1421; https://doi.org/10.3390/pharmaceutics16111421 - 6 Nov 2024
Cited by 1 | Viewed by 1658
Abstract
Objective: Colon adenocarcinoma is characterized by the downregulation of the retinoic acid receptor, making natural retinoids such as all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid effective in treatment and chemoprevention due to their ability to increase RARβ expression. However, major [...] Read more.
Objective: Colon adenocarcinoma is characterized by the downregulation of the retinoic acid receptor, making natural retinoids such as all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid effective in treatment and chemoprevention due to their ability to increase RARβ expression. However, major limitations to their use include tolerability and acquired resistance. In this study, we evaluated fenretinide, a semisynthetic derivative of all-trans retinoic acid, in an HT-29 cell line. Fenretinide was evaluated both as a free drug and encapsulated in self-assembling phosphatidylcholine nanosystems with the aim of increasing the aqueous solubility and cell availability of the drug. Methods: Fenretinide was encapsulated in lipid nanosystems obtained in water by the dispersion of an amphiphilic mixture of phospholipids, glyceryl tributyrate and polysorbate 80. The physico-chemical characterization of the nanosystems was carried out by dynamic light scattering and spectrophotometry. The biological activity was evaluated by quantitative phase imaging microscopy, MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Results: Fenretinide in phosphatidylcholine nanosystems was more active than free fenretinide in inhibiting HT-29 cells’ proliferation, as indicated by quantitative phase imaging data. Indeed, encapsulated fenretinide increased duplication time, decreased dry mass and decreased the rate of cell growth more efficiently than fenretinide. Moreover, encapsulated fenretinide effectively decreased the motility of the cells that survived the treatment. Conclusions: The results indicate that the proposed nanosystems can be considered a valuable alternative to natural retinoids in the chemoprevention and treatment of colorectal cancer. This is due to the favorable pharmacologic characteristics of fenretinide in colorectal cancer and the improved drug activity provided by nanoencapsulation. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
►▼ Show Figures

Figure 1

40 pages, 1184 KB  
Review
Enhancing Cancer Treatment Through Combined Approaches: Photodynamic Therapy in Concert with Other Modalities
by Gyeong Hong and Ji-Eun Chang
Pharmaceutics 2024, 16(11), 1420; https://doi.org/10.3390/pharmaceutics16111420 - 6 Nov 2024
Cited by 11 | Viewed by 3663
Abstract
This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT’s ability to [...] Read more.
This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT’s ability to improve therapeutic outcomes through combination strategies is examined. In cancers such as lung, breast, cholangiocarcinoma, and cervical, PDT shows promise in enhancing response rates, reducing recurrence, and minimizing adverse effects when used alongside standard modalities. This study highlights current findings on PDT’s mechanisms in complementing chemotherapy, augmenting surgical precision, and enhancing radiotherapeutic effects, thus offering a multi-faceted approach to cancer treatment. Additionally, insights into the clinical application of PDT in these cancers emphasize its potential for reducing tumor resistance and supporting more effective, personalized care. By providing an overview of PDT’s synergistic applications across diverse cancer types, this review underscores its emerging significance in oncology as a tool to address traditional treatment limitations. Ultimately, this review aims to inform and inspire researchers and clinicians seeking to refine and innovate cancer therapy strategies through PDT integration, contributing to the advancement of more effective, synergistic cancer treatments. Full article
(This article belongs to the Special Issue Progress in Photoactive Biomaterial-Based Synergistic Combination Phototherapy)
►▼ Show Figures

Figure 1

22 pages, 3522 KB  
Article
Achieving the Optimal AgO Concentrations to Modulate the Anti-Trypanosoma cruzi Activity of Ag-ZnO/AgO Nanocomposites: In Vivo Investigations
by José Rodrigues do Carmo Neto, Yarlla Loyane Lira Braga, Pablo Igor Ribeiro Franco, Jordana Fernandes de Oliveira, Rafael Obata Trevisan, Karen Martins Mendes, Milton Adriano Pelli de Oliveira, Mara Rúbia Nunes Celes, Anielle Christine Almeida Silva, Juliana Reis Machado and Marcos Vinícius da Silva
Pharmaceutics 2024, 16(11), 1415; https://doi.org/10.3390/pharmaceutics16111415 - 4 Nov 2024
Viewed by 1529
Abstract
Background/Objectives: For the development of new treatments, the acute phase of Chagas disease (CD) in experimental models acts as a filter to screen out potentially effective interventions. Therefore, the aim of this study was to evaluate ZnO nanocrystals and Ag-ZnO/AgO nanocomposites containing [...] Read more.
Background/Objectives: For the development of new treatments, the acute phase of Chagas disease (CD) in experimental models acts as a filter to screen out potentially effective interventions. Therefore, the aim of this study was to evaluate ZnO nanocrystals and Ag-ZnO/AgO nanocomposites containing different proportions of silver (ZnO:5Ag, ZnO:9Ag and ZnO:11Ag) in an experimental model of the acute phase of CD. Methods: C57Bl/6 mice were infected with 1000 forms of the Colombian strain of T. cruzi. The treatment was carried out by gavage with 5 mg/kg/d for 7 consecutive days from the first detection of parasitemia. Weight, parasitemia and survival were assessed during treatment and up to the day of euthanasia. After euthanasia, the cardiac and intestinal parasitism, inflammatory infiltrate, collagen deposition and cytokine dosages were analyzed. Results: It was observed that the nanocomposites ZnO:9Ag and ZnO:11Ag were the most effective in reducing parasitemia and increasing the survival of the infected animals. However, pure ZnO induced the maintenance of parasitemia and reduced their survival. The ZnO:9Ag and ZnO:11Ag nanocomposites were able to reduce the number of cardiac amastigote nests. In addition, they were responsible for reducing TNF-α and IL-6 in situ. ZnO:9Ag and ZnO:11Ag induced a reduction in the intestinal inflammatory infiltrate and neuronal protection in the myenteric plexus, as well as reducing TNF-α in situ. Conclusions: Based on these results, it is suggested that there is an ideal concentration in terms of the proportion of Ag/AgO and ZnO in nanocomposites for use against CD. Thus, ZnO:9Ag or ZnO:11Ag nanomaterials are potential candidates for the development of new biotechnological products for the therapy of CD. Full article
(This article belongs to the Special Issue Anti-parasitic Applications of Nanoparticles)
►▼ Show Figures

Graphical abstract

29 pages, 3207 KB  
Review
Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery
by Sofia Brito, Moonki Baek and Bum-Ho Bin
Pharmaceutics 2024, 16(11), 1403; https://doi.org/10.3390/pharmaceutics16111403 - 31 Oct 2024
Cited by 18 | Viewed by 14671
Abstract
Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare [...] Read more.
Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field. Full article
(This article belongs to the Special Issue Transdermal Delivery: Challenges and Opportunities)
►▼ Show Figures

Figure 1

21 pages, 1128 KB  
Review
Pharmacological Treatment of Interstitial Lung Diseases: A Novel Landscape for Inhaled Agents
by Vito D’Agnano, Fabio Perrotta, Ramona Fomez, Valerio Maria Carrozzo, Angela Schiattarella, Stefano Sanduzzi Zamparelli, Raffaella Pagliaro, Andrea Bianco and Domenica Francesca Mariniello
Pharmaceutics 2024, 16(11), 1391; https://doi.org/10.3390/pharmaceutics16111391 - 29 Oct 2024
Cited by 3 | Viewed by 3589
Abstract
Interstitial lung diseases (ILDs) encompass a heterogeneous group of over 200 disorders that require individualized treatment. Antifibrotic agents, such as nintedanib and pirfenidone, have remarkably revolutionized the treatment landscape of patients with idiopathic pulmonary fibrosis (IPF). Moreover, the approval of nintedanib has also [...] Read more.
Interstitial lung diseases (ILDs) encompass a heterogeneous group of over 200 disorders that require individualized treatment. Antifibrotic agents, such as nintedanib and pirfenidone, have remarkably revolutionized the treatment landscape of patients with idiopathic pulmonary fibrosis (IPF). Moreover, the approval of nintedanib has also expanded the therapeutic options for patients with progressive pulmonary fibrosis other than IPF. However, despite recent advances, current therapeutic strategies based on antifibrotic agents and/or immunomodulation are associated with non-negligible side effects. Therefore, several studies have explored the inhalation route aiming to spread higher local concentrations while limiting systemic toxicity. In this review, we examined the currently available literature about preclinical and clinical studies testing the efficacy and safety of inhalation-based antifibrotics, immunomodulatory agents, antioxidants, mucolytics, bronchodilators, and vasodilator agents in ILDs. Full article
(This article belongs to the Special Issue Inhalable Drugs for the Treatment of Chronic Respiratory Diseases)
►▼ Show Figures

Figure 1

20 pages, 5663 KB  
Article
A Novel Poly(ε-Caprolactone)-Based Photo-Crosslinkable Liquid Copolymer as a Versatile Drug Delivery Platform
by Marcus Flowers, Nicole Mertens, Amanda Billups, Brenda M. Ogle and Chun Wang
Pharmaceutics 2024, 16(11), 1380; https://doi.org/10.3390/pharmaceutics16111380 - 27 Oct 2024
Viewed by 1847
Abstract
Background/Objectives: Hydrophobic semi-solid or liquid biodegradable polymers have shown unique advantages as injectable matrices for sustained release of a wide range of drugs. Here we report the design, synthesis, and characterization of a new low-melt liquid copolymer based on poly(ε-caprolactone) (PCL) and [...] Read more.
Background/Objectives: Hydrophobic semi-solid or liquid biodegradable polymers have shown unique advantages as injectable matrices for sustained release of a wide range of drugs. Here we report the design, synthesis, and characterization of a new low-melt liquid copolymer based on poly(ε-caprolactone) (PCL) and establish its utility as a versatile delivery platform. Methods: The copolymer, mPA20, consisting of short PCL blocks connected via acid-labile acetal linkages, was synthesized using a one-pot reaction and its properties were comprehensively characterized. Results: mPA20 is an amorphous, injectable liquid at physiological temperature and can undergo pH-sensitive hydrolytic degradation. mPA20 bearing methacrylate end groups can be photo-crosslinked into solid matrices with tunable mechanical properties. A hydrophobic fluorophore, Nile Red (NR), was solubilized in mPA20 without any solvent. Sustained release of NR into aqueous medium was achieved using mPA20, either as an injectable liquid depot or a photo-crosslinked solid matrix. Further, mPA20 self-emulsified in water to form nanodroplets, which were subsequently photo-crosslinked into nanogels. Both the nanodroplets and nanogels mediated efficient intracellular delivery of NR with no cytotoxicity. Conclusions: mPA20, a new photo-crosslinkable, hydrophobic liquid copolymer with pH-sensitive degradability, is highly adaptable as either an injectable or implantable depot or nanoscale carrier for the controlled release and intracellular delivery of poorly soluble drugs. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
►▼ Show Figures

Figure 1

51 pages, 3047 KB  
Review
The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems
by Nargish Parvin, Tapas K. Mandal and Sang-Woo Joo
Pharmaceutics 2024, 16(11), 1366; https://doi.org/10.3390/pharmaceutics16111366 - 25 Oct 2024
Cited by 6 | Viewed by 4315
Abstract
The COVID-19 pandemic has significantly accelerated progress in RNA-based therapeutics, particularly through the successful development and global rollout of mRNA vaccines. This review delves into the transformative impact of the pandemic on RNA therapeutics, with a strong focus on lipid nanoparticles (LNPs) as [...] Read more.
The COVID-19 pandemic has significantly accelerated progress in RNA-based therapeutics, particularly through the successful development and global rollout of mRNA vaccines. This review delves into the transformative impact of the pandemic on RNA therapeutics, with a strong focus on lipid nanoparticles (LNPs) as a pivotal delivery platform. LNPs have proven to be critical in enhancing the stability, bioavailability, and targeted delivery of mRNA, facilitating the unprecedented success of vaccines like those developed by Pfizer-BioNTech and Moderna. Beyond vaccines, LNP technology is being explored for broader therapeutic applications, including treatments for cancer, rare genetic disorders, and infectious diseases. This review also discusses emerging RNA delivery systems, such as polymeric nanoparticles and viral vectors, which offer alternative strategies to overcome existing challenges related to stability, immune responses, and tissue-specific targeting. Additionally, we examine the pandemic’s influence on regulatory processes, including the fast-tracked approvals for RNA therapies, and the surge in research funding that has spurred further innovation in the field. Public acceptance of RNA-based treatments has also grown, laying the groundwork for future developments in personalized medicine. By providing an in-depth analysis of these advancements, this review highlights the long-term impact of COVID-19 on the evolution of RNA therapeutics and the future of precision drug delivery technologies. Full article
(This article belongs to the Special Issue Advanced Materials Science and Technology in Drug Delivery)
►▼ Show Figures

Figure 1

31 pages, 3958 KB  
Review
Emerging Cationic Nanovaccines
by Ana Maria Carmona-Ribeiro and Yunys Pérez-Betancourt
Pharmaceutics 2024, 16(11), 1362; https://doi.org/10.3390/pharmaceutics16111362 - 25 Oct 2024
Cited by 3 | Viewed by 2376
Abstract
Cationic vaccines of nanometric sizes can directly perform the delivery of antigen(s) and immunomodulator(s) to dendritic cells in the lymph nodes. The positively charged nanovaccines are taken up by antigen-presenting cells (APCs) of the lymphatic system often originating the cellular immunological defense required [...] Read more.
Cationic vaccines of nanometric sizes can directly perform the delivery of antigen(s) and immunomodulator(s) to dendritic cells in the lymph nodes. The positively charged nanovaccines are taken up by antigen-presenting cells (APCs) of the lymphatic system often originating the cellular immunological defense required to fight intracellular microbial infections and the proliferation of cancers. Cationic molecules imparting the positive charges to nanovaccines exhibit a dose-dependent toxicity which needs to be systematically addressed. Against the coronavirus, mRNA cationic nanovaccines evolved rapidly. Nowadays cationic nanovaccines have been formulated against several infections with the advantage of cationic compounds granting protection of nucleic acids in vivo against biodegradation by nucleases. Up to the threshold concentration of cationic molecules for nanovaccine delivery, cationic nanovaccines perform well eliciting the desired Th 1 improved immune response in the absence of cytotoxicity. A second strategy in the literature involves dilution of cationic components in biocompatible polymeric matrixes. Polymeric nanoparticles incorporating cationic molecules at reduced concentrations for the cationic component often result in an absence of toxic effects. The progress in vaccinology against cancer involves in situ designs for cationic nanovaccines. The lysis of transformed cancer cells releases several tumoral antigens, which in the presence of cationic nanoadjuvants can be systemically presented for the prevention of metastatic cancer. In addition, these local cationic nanovaccines allow immunotherapeutic tumor treatment. Full article
(This article belongs to the Special Issue Applications of Nanomaterials in Immunotherapies)
►▼ Show Figures

Figure 1

16 pages, 2988 KB  
Article
Customizable Self-Microemulsifying Rectal Suppositories by Semisolid Extrusion 3D Printing
by Hye Jin Park and Dong Wuk Kim
Pharmaceutics 2024, 16(11), 1359; https://doi.org/10.3390/pharmaceutics16111359 - 24 Oct 2024
Cited by 4 | Viewed by 2318
Abstract
Objectives: This study aims to create an innovative self-microemulsifying drug delivery system (SMEDDS) suppository for ibuprofen (IBU) using semisolid extrusion (SSE) three-dimensional (3D) printing technology. Methods: Based on solubility studies and the ability to form a transparent microemulsion upon dilution, a [...] Read more.
Objectives: This study aims to create an innovative self-microemulsifying drug delivery system (SMEDDS) suppository for ibuprofen (IBU) using semisolid extrusion (SSE) three-dimensional (3D) printing technology. Methods: Based on solubility studies and the ability to form a transparent microemulsion upon dilution, a selected oil, surfactant, and co-surfactant were utilized to prepare SMEDDS-3DPS containing IBU. The optimal formulation consisted of 10% Triacetin, 80% Gelucire 48/16, and 10% Tetraethylene glycol. SSE 3D printing was employed to create three different-sized suppositories with varying drug contents. These suppositories were assessed for their physicochemical properties, content uniformity, and dissolution profiles. Results: The prepared mixture exhibited suitable physical properties for printing, with nano-sized emulsion droplets providing a large surface area for improved drug absorption in the rectum. Characterization techniques such as differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy indicated that IBU was present in the formulation in an amorphous state. Additionally, in vitro dissolution tests demonstrated that SMEDDS-3DPS had a significantly higher initial dissolution rate compared with IBU powder. Conclusions: This research suggests that SMEDDS-3DPS, as a rectal IBU dosage form, can enhance the rectal bioavailability of IBU. It demonstrates the versatility of 3D printing as a novel manufacturing method for lipid-based suppositories and highlights the simplicity and adaptability of SSE 3D printing technology in producing customized suppositories tailored to individual patient needs, surpassing traditional methods. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
►▼ Show Figures

Graphical abstract

27 pages, 8072 KB  
Article
Preparation of Ibuprofen-Loaded Inhalable γCD-MOFs by Freeze-Drying Using the QbD Approach
by Anett Motzwickler-Németh, Petra Party, Péter Simon, Milena Sorrenti, Rita Ambrus and Ildikó Csóka
Pharmaceutics 2024, 16(11), 1361; https://doi.org/10.3390/pharmaceutics16111361 - 24 Oct 2024
Cited by 6 | Viewed by 1554
Abstract
Background/Objectives: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery—expressly in the lung—seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin [...] Read more.
Background/Objectives: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery—expressly in the lung—seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin (γCD) and potassium cations (K+) were employed to encapsulate the poorly water-soluble model drug Ibuprofen (IBU) for the treatment of cystic fibrosis (CF). Methods: Using the LeanQbD® software (v2022), we designed the experiments based on the Quality by Design (QbD) concept. According to QbD, we identified the three most critical factors, which were the molar ratio of the IBU to the γCD, incubation time, and the percentage of the organic solvent. light-, scanning electron microscope (SEM) and laser diffraction were utilized to observe the morphology and particle size of the samples. In addition, the products were characterized by Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Results: Based on characterizations, we concluded that a γCD-MOF/IBU complex was also formed using the freeze-drying method. Using formulations with optimal aerodynamic properties, we achieved 38.10 ± 5.06 and 47.18 ± 4.18 Fine Particle Fraction% (FPF%) based on the Andersen Cascade Impactor measurement. With these formulations, we achieved a fast dissolution profile and increased IBU solubility. Conclusions: This research successfully demonstrates the innovative use of freeze-drying to produce γCD-MOFs for inhalable IBU delivery. The method enabled to modify the particle size, which was crucial for successful pulmonary intake, emphasizing the need for further investigation of these formulations as effective delivery systems. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
►▼ Show Figures

Figure 1

14 pages, 4946 KB  
Article
Pediatric Orally Disintegrating Tablets (ODTs) with Enhanced Palatability Based on Propranolol HCl Coground with Hydroxypropyl-β-Cyclodextrin
by Marzia Cirri, Paola A. Mura, Francesca Maestrelli, Simona Benedetti and Susanna Buratti
Pharmaceutics 2024, 16(11), 1351; https://doi.org/10.3390/pharmaceutics16111351 - 23 Oct 2024
Cited by 4 | Viewed by 2367
Abstract
Background: Propranolol, largely prescribed as an antihypertensive and antiarrhythmic drug in pediatrics, is characterized by a bitter taste and an astringent aftertaste. Currently, the therapy requires crushing of tablets for adults and their dispersion in water many times a day, leading to loss [...] Read more.
Background: Propranolol, largely prescribed as an antihypertensive and antiarrhythmic drug in pediatrics, is characterized by a bitter taste and an astringent aftertaste. Currently, the therapy requires crushing of tablets for adults and their dispersion in water many times a day, leading to loss of dosing accuracy, low palatability, and poor compliance for both patients and caregivers. Objectives: This work aimed to exploit cyclodextrin complexation by cogrinding to develop orally disintegrating tablets (ODTs) endowed with reliable dosing accuracy, good palatability and safety, ease of swallowability, and ultimately better compliance for both pediatric patients and caregivers. Results: Different formulation variables and process parameters were evaluated in preparing ODTs. The technological and morphological characterization and disintegration tests were performed according to official and alternative tests to select the ODT formulation based on the drug Hydroxypropyl-β-cyclodextrin (HPβCD) coground complex form containing Pearlitol® Flash as the diluent and 8% Explotab® as the superdisintegrant, which demonstrated the highest % drug dissolution in simulated saliva and acceptable in vitro palatability assessed by the electronic tongue, confirming the good taste-masking power of HPβCD towards propranolol. Conclusions: Such a new dosage form of propranolol could represent a valid alternative to the common extemporaneous preparations, overcoming the lack of solid formulations of propranolol intended for pediatric use. Full article
(This article belongs to the Special Issue Orally Disintegrating Dosage Forms Based on Cyclodextrins and Hydrophilic Polymers)
►▼ Show Figures

Figure 1

18 pages, 2665 KB  
Article
The Key Role of Wettability and Boundary Layer in Dissolution Rate Test
by Alice Biasin, Federico Pribac, Erica Franceschinis, Angelo Cortesi, Lucia Grassi, Dario Voinovich, Italo Colombo, Gabriele Grassi, Gesmi Milcovich, Mario Grassi and Michela Abrami
Pharmaceutics 2024, 16(10), 1335; https://doi.org/10.3390/pharmaceutics16101335 - 18 Oct 2024
Cited by 1 | Viewed by 1696
Abstract
Background/Objectives: The present work proposes a mathematical model able to describe the dissolution of poly-disperse drug spherical particles in a solution (Dissolution Rate Test—DRT). DRT is a pivotal test performed in the pharmaceutical field to qualitatively assess drug bioavailability. Methods: The proposed mathematical [...] Read more.
Background/Objectives: The present work proposes a mathematical model able to describe the dissolution of poly-disperse drug spherical particles in a solution (Dissolution Rate Test—DRT). DRT is a pivotal test performed in the pharmaceutical field to qualitatively assess drug bioavailability. Methods: The proposed mathematical model relies on the key hallmarks of DRT, such as particle size distribution, solubility, wettability, hydrodynamic conditions in the dissolving liquid of finite dimensions, and possible re-crystallization during the dissolution process. The spherical shape of the drug particles was the only cue simplification applied. Two model drugs were considered to check model robustness: theophylline (both soluble and wettable) and praziquantel (both poorly soluble and wettable). Results: The DRT data analysis within the proposed model allows us to understand that for theophylline, the main resistance to dissolution is due to the boundary layer surrounding drug particles, whereas wettability plays a negligible role. Conversely, the effect of low wettability cannot be neglected for praziquantel. These results are validated by the determination of drug wettability performed while measuring the solid–liquid contact angle on four liquids with decreasing polarities. Moreover, the percentage of drug polarity was determined. Conclusions: The proposed mathematical model confirms the importance of the different physical phenomena leading the dissolution of poly-disperse solid drug particles in a solution. Although a comprehensive mathematical model was proposed and applied, the DRT data of theophylline and praziquantel was successfully fitted by means of just two fitting parameters. Full article
(This article belongs to the Special Issue Mathematical Modeling in Drug Delivery)
►▼ Show Figures

Graphical abstract

16 pages, 5063 KB  
Article
Respiratory Delivery of Lacticaseibacillus rhamnosus GG by Vibrating-Mesh and Jet Nebulisation
by Alex Seungyeon Byun, Luis Vitetta, Hak-Kim Chan and Philip Chi Lip Kwok
Pharmaceutics 2024, 16(10), 1326; https://doi.org/10.3390/pharmaceutics16101326 - 14 Oct 2024
Viewed by 3484
Abstract
Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics. Objectives: This study aimed to investigate [...] Read more.
Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics. Objectives: This study aimed to investigate whether nebulisation is suitable for delivering Lacticaseibacillus rhamnosus GG (LGG) into the lungs for the potential treatment of bacterial pulmonary infections. Methods: It compared the dose output and aerosol performance of a vibrating-mesh nebuliser (VMN) and a jet nebuliser (JN) in nebulising LGG suspended in de Man Rogosa Sharpe (MRS) broth, phosphate-buffered saline (PBS), or normal saline (0.9% w/v sodium chloride in water). Results: The VMN consistently produced a higher output than the JN for all liquid media, indicating that VMN was more efficient. The fine-particle fractions of both nebulisers were comparable for a given medium. The highest fine-particle fraction was achieved with LGG suspended in MRS broth for both nebulisers (20.5 ± 2.8% for VMN; 18.7 ± 3.4% for JN). This suggests that the aerosol performance of nebulised probiotics may depend on the medium in which the probiotic bacteria were suspended. Conclusions: Therefore, this study demonstrated that the nebulisation efficiency of LGG depended on the nebuliser type and liquid medium of the probiotic suspension. Full article
(This article belongs to the Special Issue Inhaled Treatment of Respiratory Infections, 2nd Edition)
►▼ Show Figures

Figure 1

27 pages, 2107 KB  
Review
Artificial Intelligence (AI) Applications in Drug Discovery and Drug Delivery: Revolutionizing Personalized Medicine
by Dolores R. Serrano, Francis C. Luciano, Brayan J. Anaya, Baris Ongoren, Aytug Kara, Gracia Molina, Bianca I. Ramirez, Sergio A. Sánchez-Guirales, Jesus A. Simon, Greta Tomietto, Chrysi Rapti, Helga K. Ruiz, Satyavati Rawat, Dinesh Kumar and Aikaterini Lalatsa
Pharmaceutics 2024, 16(10), 1328; https://doi.org/10.3390/pharmaceutics16101328 - 14 Oct 2024
Cited by 127 | Viewed by 37413
Abstract
Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the [...] Read more.
Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others. While the integration of AI promises to enhance efficiency, reduce costs, and improve both medicines and patient health, it also raises important questions from a regulatory point of view. In this review article, we will present a comprehensive overview of AI’s applications in the pharmaceutical industry, covering areas such as drug discovery, target optimization, personalized medicine, drug safety, and more. By analyzing current research trends and case studies, we aim to shed light on AI’s transformative impact on the pharmaceutical industry and its broader implications for healthcare. Full article
(This article belongs to the Special Issue Computational Intelligence (CI) Tools in Applications of Pharmaceutics)
►▼ Show Figures

Figure 1

17 pages, 1313 KB  
Review
Serum Albumin in Nasal Drug Delivery Systems: Exploring the Role and Application
by Sandra Aulia Mardikasari, Gábor Katona and Ildikó Csóka
Pharmaceutics 2024, 16(10), 1322; https://doi.org/10.3390/pharmaceutics16101322 - 11 Oct 2024
Cited by 6 | Viewed by 4021
Abstract
The application of serum albumin in various types of formulations has emerged as a valuable option in biomedical research, especially in the field of nasal drug delivery systems. A serum albumin-based carrier system has been employed due to several benefits, such as enhancing [...] Read more.
The application of serum albumin in various types of formulations has emerged as a valuable option in biomedical research, especially in the field of nasal drug delivery systems. A serum albumin-based carrier system has been employed due to several benefits, such as enhancing drug solubility and stability, generating the desired controlled release profile, and developing favorable properties with respect to the challenges in nasal conditions, which, in this case, involves hindering rapid elimination due to nasal mucociliary clearance. Accordingly, considering the important role of serum albumin, in-depth knowledge related to its utilization in preparing nasal drug formulation is highly encouraged. This review aimed to explore the potential application of serum albumin in fabricating nasal drug formulations and its crucial role and functionality regarding the binding interaction with nasal mucin, which significantly determines the successful administration of nasal drug formulations. Full article
(This article belongs to the Special Issue Topical Advisory Panel Members' Collection Series: Nanocarriers for Alternative Drug Delivery)
►▼ Show Figures

Graphical abstract

15 pages, 1828 KB  
Article
Model-Informed Precision Dosing for Personalized Ustekinumab Treatment in Plaque Psoriasis
by Karine Rodríguez-Fernández, Javier Zarzoso-Foj, Marina Saez-Bello, Almudena Mateu-Puchades, Antonio Martorell-Calatayud, Matilde Merino-Sanjuan, Elena Gras-Colomer, Monica Climente-Martí and Victor Mangas-Sanjuan
Pharmaceutics 2024, 16(10), 1295; https://doi.org/10.3390/pharmaceutics16101295 - 4 Oct 2024
Cited by 2 | Viewed by 1933
Abstract
Background/Objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting [...] Read more.
Background/Objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting clinical dose selection decisions. Methods: This study proposes a methodology to individualize ustekinumab (UTK) dosing strategies for 23 Spanish patients with moderate to severe chronic plaque psoriasis., considering the uncertainty of individual parameters within a population PK/PD model. Results: An indirect response model from previous research was used to describe the PK/PD relationship between UTK serum concentrations and the Psoriasis Area and Severity Index (PASI) score. A maximum inhibition drug effect (Imax) model was selected, and a first-order remission constant rate of psoriatic skin lesion (kout = 0.016 d−1) was estimated. Conclusions: The MIPD approach predicted that 35% and 26% of the patients would need an optimized and intensified dosage regimen, respectively, compared to the regimen typically used in clinical practice. This analysis demonstrated its utility as a tool for selecting personalized UTK dosing regimens in clinical practice in order to optimize the probability of achieving targeted clinical outcomes in patients with psoriasis. Full article
(This article belongs to the Special Issue Population Pharmacokinetics and Its Clinical Applications)
►▼ Show Figures

Figure 1

14 pages, 2945 KB  
Article
Application of the Thermal Analysis of Frozen Aqueous Solutions to Assess the Miscibility of Hyaluronic Acid and Polymers Used for Dissolving Microneedles
by Ken-ichi Izutsu, Hiroyuki Yoshida, Yasuhiro Abe, Eiichi Yamamoto, Yoji Sato and Daisuke Ando
Pharmaceutics 2024, 16(10), 1280; https://doi.org/10.3390/pharmaceutics16101280 - 30 Sep 2024
Cited by 1 | Viewed by 1657
Abstract
Background: The combination of multiple polymers is anticipated to serve as a means to diversify the physical properties and functionalities of dissolving microneedles. The mixing state of components is considered as a crucial factor in determining their suitability. Objectives: The purpose of this [...] Read more.
Background: The combination of multiple polymers is anticipated to serve as a means to diversify the physical properties and functionalities of dissolving microneedles. The mixing state of components is considered as a crucial factor in determining their suitability. Objectives: The purpose of this study was to elucidate whether thermal analysis of frozen aqueous solutions can appropriately predict the miscibility of hyaluronic acid (HA) and other polymers used for dissolving microneedles prepared by a micromolding method. Methods: Aliquots of aqueous polymer solutions were applied for thermal analysis by heating the samples from −70 °C at 5 °C/min to obtain the transition temperature of amorphous polymers and/or the crystallization/melting peaks of polymers (e.g., polyethylene glycol (PEG)). Films and dissolving microneedles were prepared by air-drying of the aqueous polymer solutions to assess the polymer miscibility in the solids. Results: The frozen aqueous single-solute HA solutions exhibited a clear Tg′ (the glass transition temperature of maximally freeze-concentrated solutes) at approximately −20 °C. The combination of HA with several polymers (e.g., dextran FP40, DEAE-dextran, dextran sulfate, and gelatin) showed a single Tg′ transition at temperatures that shifted according to their mass ratio, which strongly suggested the mixing of the freeze-concentrated solutes. By contrast, the observation of two Tg′ transitions in a scan strongly suggested the separation of HA and polyvinylpyrrolidone (PVP) or HA and polyacrylic acid (PAA) into different freeze-concentrated phases, each of which was rich in an amorphous polymer. The combination of HA and PEG exhibited the individual physical changes of the polymers. The polymer combinations that showed phase separation in the frozen solution formed opaque films and microneedles upon their preparation by air-drying. Coacervation occurring in certain polymer combinations was also suggested as a factor contributing to the formation of cloudy films. Conclusions: Freezing aqueous polymer solutions creates a highly concentrated polymer environment that mimics the matrix of dissolving microneedles prepared through air drying. This study demonstrated that thermal analysis of the frozen solution offers insights into the mixing state of condensed polymers, which can be useful for predicting the physical properties of microneedles. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
►▼ Show Figures

Graphical abstract

15 pages, 4021 KB  
Article
Feasibility of a High-Dose Inhaled Indomethacin Dry Powder with Dual Deposition for Pulmonary and Oral Delivery
by Jamie E. Spahn, Amr Hefnawy, Feng Zhang and Hugh D. C. Smyth
Pharmaceutics 2024, 16(10), 1269; https://doi.org/10.3390/pharmaceutics16101269 - 28 Sep 2024
Cited by 1 | Viewed by 1607
Abstract
In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with [...] Read more.
In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
►▼ Show Figures

Graphical abstract

23 pages, 2778 KB  
Review
Self-Tumor Antigens in Solid Tumors Turned into Vaccines by α-gal Micelle Immunotherapy
by Uri Galili
Pharmaceutics 2024, 16(10), 1263; https://doi.org/10.3390/pharmaceutics16101263 - 27 Sep 2024
Cited by 2 | Viewed by 2427
Abstract
A major reason for the failure of the immune system to detect tumor antigens (TAs) is the insufficient uptake, processing, and presentation of TAs by antigen-presenting cells (APCs). The immunogenicity of TAs in the individual patient can be markedly increased by the in [...] Read more.
A major reason for the failure of the immune system to detect tumor antigens (TAs) is the insufficient uptake, processing, and presentation of TAs by antigen-presenting cells (APCs). The immunogenicity of TAs in the individual patient can be markedly increased by the in situ targeting of tumor cells for robust uptake by APCs, without the need to identify and characterize the TAs. This is feasible by the intra-tumoral injection of α-gal micelles comprised of glycolipids presenting the carbohydrate-antigen “α-gal epitope” (Galα1-3Galβ1-4GlcNAc-R). Humans produce a natural antibody called “anti-Gal” (constituting ~1% of immunoglobulins), which binds to α-gal epitopes. Tumor-injected α-gal micelles spontaneously insert into tumor cell membranes, so that multiple α-gal epitopes are presented on tumor cells. Anti-Gal binding to these epitopes activates the complement system, resulting in the killing of tumor cells, and the recruitment of multiple APCs (dendritic cells and macrophages) into treated tumors by the chemotactic complement cleavage peptides C5a and C3a. In this process of converting the treated tumor into a personalized TA vaccine, the recruited APC phagocytose anti-Gal opsonized tumor cells and cell membranes, process the internalized TAs and transport them to regional lymph-nodes. TA peptides presented on APCs activate TA-specific T cells to proliferate and destroy the metastatic tumor cells presenting the TAs. Studies in anti-Gal-producing mice demonstrated the induction of effective protection against distant metastases of the highly tumorigenic B16 melanoma following injection of natural and synthetic α-gal micelles into primary tumors. This treatment was further found to synergize with checkpoint inhibitor therapy by the anti-PD1 antibody. Phase-1 clinical trials indicated that α-gal micelle immunotherapy is safe and can induce the infiltration of CD4+ and CD8+ T cells into untreated distant metastases. It is suggested that, in addition to converting treated metastases into an autologous TA vaccine, this treatment should be considered as a neoadjuvant therapy, administering α-gal micelles into primary tumors immediately following their detection. Such an immunotherapy will convert tumors into a personalized anti-TA vaccine for the period prior to their resection. Full article
(This article belongs to the Special Issue Nanomedicines for Overcoming Tumor Immunotherapy Tolerance)
►▼ Show Figures

Figure 1

13 pages, 966 KB  
Review
Topical Application of Centella asiatica in Wound Healing: Recent Insights into Mechanisms and Clinical Efficacy
by Katarzyna Witkowska, Magdalena Paczkowska-Walendowska, Ewa Garbiec and Judyta Cielecka-Piontek
Pharmaceutics 2024, 16(10), 1252; https://doi.org/10.3390/pharmaceutics16101252 - 26 Sep 2024
Cited by 21 | Viewed by 20282
Abstract
Centella asiatica, widely known as Gotu kola, is a traditional herb celebrated for its benefits in skin health and wound healing. Recent research has provided new insights into its efficacy, particularly through topical applications. This review highlights the plant’s mechanisms, focusing [...] Read more.
Centella asiatica, widely known as Gotu kola, is a traditional herb celebrated for its benefits in skin health and wound healing. Recent research has provided new insights into its efficacy, particularly through topical applications. This review highlights the plant’s mechanisms, focusing on its active compounds such as asiaticoside, madecassoside, asiatic acid, and madecassic acid, which enhance collagen synthesis, modulate inflammation, and offer antioxidant protection. Clinical trials have been collected and summarized that innovative delivery systems, such as hydrogels, nanostructures or microneedles, can accelerate wound healing, reduce wound size, and improve recovery times in various wound types, including diabetic ulcers and burns. Future research will likely refine these technologies and explore new applications, reinforcing the role of C. asiatica in contemporary wound care. Advances in formulation and delivery will continue to enhance the plant’s therapeutic potential, offering promising solutions for effective wound management. Full article
(This article belongs to the Special Issue Therapeutic Approaches for Wound-Associated Skin Diseases)
►▼ Show Figures

Figure 1

22 pages, 6892 KB  
Review
Review on Photoacoustic Monitoring after Drug Delivery: From Label-Free Biomarkers to Pharmacokinetics Agents
by Jiwoong Kim, Seongwook Choi, Chulhong Kim, Jeesu Kim and Byullee Park
Pharmaceutics 2024, 16(10), 1240; https://doi.org/10.3390/pharmaceutics16101240 - 24 Sep 2024
Cited by 6 | Viewed by 2294
Abstract
Photoacoustic imaging (PAI) is an emerging noninvasive and label-free method for capturing the vasculature, hemodynamics, and physiological responses following drug delivery. PAI combines the advantages of optical and acoustic imaging to provide high-resolution images with multiparametric information. In recent decades, PAI’s abilities have [...] Read more.
Photoacoustic imaging (PAI) is an emerging noninvasive and label-free method for capturing the vasculature, hemodynamics, and physiological responses following drug delivery. PAI combines the advantages of optical and acoustic imaging to provide high-resolution images with multiparametric information. In recent decades, PAI’s abilities have been used to determine reactivity after the administration of various drugs. This study investigates photoacoustic imaging as a label-free method of monitoring drug delivery responses by observing changes in the vascular system and oxygen saturation levels across various biological tissues. In addition, we discuss photoacoustic studies that monitor the biodistribution and pharmacokinetics of exogenous contrast agents, offering contrast-enhanced imaging of diseased regions. Finally, we demonstrate the crucial role of photoacoustic imaging in understanding drug delivery mechanisms and treatment processes. Full article
(This article belongs to the Special Issue Advanced Materials Science and Technology in Drug Delivery)
►▼ Show Figures

Figure 1

23 pages, 4533 KB  
Article
Exploring Cationic Guar Gum: Innovative Hydrogels and Films for Enhanced Wound Healing
by Kamila Gabrieli Dallabrida, Willer Cezar Braz, Crisleine Marchiori, Thainá Mayer Alves, Luiza Stolz Cruz, Giovanna Araujo de Morais Trindade, Patrícia Machado, Lucas Saldanha da Rosa, Najeh Maissar Khalil, Fabiane Gomes de Moraes Rego, André Ricardo Fajardo, Luana Mota Ferreira, Marcel Henrique Marcondes Sari and Jéssica Brandão Reolon
Pharmaceutics 2024, 16(9), 1233; https://doi.org/10.3390/pharmaceutics16091233 - 22 Sep 2024
Cited by 12 | Viewed by 3394
Abstract
Background/Objectives: This study developed and characterized hydrogels (HG-CGG) and films (F-CGG) based on cationic guar gum (CGG) for application in wound healing. Methods: HG-CGG (2% w/v) was prepared by gum thickening and evaluated for pH, stability, spreadability, and viscosity. F-CGG [...] Read more.
Background/Objectives: This study developed and characterized hydrogels (HG-CGG) and films (F-CGG) based on cationic guar gum (CGG) for application in wound healing. Methods: HG-CGG (2% w/v) was prepared by gum thickening and evaluated for pH, stability, spreadability, and viscosity. F-CGG was obtained using an aqueous dispersion of CGG (6% w/v) and the solvent casting method. F-CGG was characterized for thickness, weight uniformity, morphology, mechanical properties, hydrophilicity, and swelling potential. Both formulations were evaluated for bioadhesive potential on intact and injured porcine skin, as well as antioxidant activity. F-CGG was further studied for biocompatibility using hemolysis and cell viability assays (L929 fibroblasts), and its wound-healing potential by the scratch assay. Results: HG-CGG showed adequate viscosity and spreadability profiles for wound coverage, but its bioadhesive strength was reduced on injured skin. In contrast, F-CGG maintained consistent bioadhesive strength regardless of skin condition (6554.14 ± 540.57 dyne/cm2 on injured skin), presenting appropriate mechanical properties (flexible, transparent, thin, and resistant) and a high swelling capacity (2032 ± 211% after 6 h). F-CGG demonstrated superior antioxidant potential compared to HG-CGG (20.50 mg/mL ABTS+ radical scavenging activity), in addition to exhibiting low hemolytic potential and no cytotoxicity to fibroblasts. F-CGG promoted the proliferation of L929 cells in vitro, supporting wound healing. Conclusions: Therefore, CGG proved to be a promising material for developing formulations with properties suitable for cutaneous use. F-CGG combines bioadhesion, antioxidant activity, biocompatibility, cell proliferation, and potential wound healing, making it promising for advanced wound treatment. Full article
(This article belongs to the Special Issue Research on the Development of Nano-Based Polymeric Films for Drugs and Their Derivatives)
►▼ Show Figures

Figure 1

15 pages, 2077 KB  
Article
Oral Gels as an Alternative to Liquid Pediatric Suspensions Compounded from Commercial Tablets
by Monika Trofimiuk, Małgorzata Sznitowska and Katarzyna Winnicka
Pharmaceutics 2024, 16(9), 1229; https://doi.org/10.3390/pharmaceutics16091229 - 20 Sep 2024
Cited by 1 | Viewed by 1834
Abstract
The aim of the study was to propose pharmacy-compounded oral gels as a new and alternative dosage form that is attractive to children as having a better masking taste than syrups and reducing the risk of spilling. The application and physical properties of [...] Read more.
The aim of the study was to propose pharmacy-compounded oral gels as a new and alternative dosage form that is attractive to children as having a better masking taste than syrups and reducing the risk of spilling. The application and physical properties of the gels prepared with cellulose derivatives (hydroxyethylcellulose and carmellose sodium) or carbomers were evaluated. The results of the study showed the most suitable consistency, viscosity, and organoleptic properties for gels prepared with carbomer and cellulose derivatives at concentrations of 0.75% and 2.0%, respectively. The microbial stability of the gels was guaranteed by the use of methylparaben and potassium sorbate. VAL (valsartan) and CC (candesartan cilexetil) tablets, often used off-label in children, were pulverized and suspended in the hydrogel bases, resulting in final drug concentrations of 4 mg/g and 1 mg/g, respectively. There was no significant change in viscosity and consistency parameters when the pulverized tablets were added, and only small changes in viscosity and consistency were observed during 35 days of storage, especially in the gels with sodium carmellose and candesartan. On the basis of the drug assay, an expiry date of 25 °C was recommended: 35 days for valsartan and 14 days for candesartan preparations. Full article
(This article belongs to the Special Issue Extemporaneous Formulations: Filling the Gap in the Pharmaceutical Industry with Personalized Medicines)
►▼ Show Figures

Figure 1

15 pages, 4031 KB  
Article
Magnetic Nanoparticles with On-Site Azide and Alkyne Functionalized Polymer Coating in a Single Step through a Solvothermal Process
by Romualdo Mora-Cabello, David Fuentes-Ríos, Lidia Gago, Laura Cabeza, Ana Moscoso, Consolación Melguizo, José Prados, Francisco Sarabia and Juan Manuel López-Romero
Pharmaceutics 2024, 16(9), 1226; https://doi.org/10.3390/pharmaceutics16091226 - 19 Sep 2024
Cited by 3 | Viewed by 2170
Abstract
Background/Objectives: Magnetic Fe3O4 nanoparticles (MNPs) are becoming more important every day. We prepared MNPs in a simple one-step reaction by following the solvothermal method, assisted by azide and alkyne functionalized polyethylene glycol (PEG400) polymers, as well as by PEG6000 [...] Read more.
Background/Objectives: Magnetic Fe3O4 nanoparticles (MNPs) are becoming more important every day. We prepared MNPs in a simple one-step reaction by following the solvothermal method, assisted by azide and alkyne functionalized polyethylene glycol (PEG400) polymers, as well as by PEG6000 and the polyol β-cyclodextrin (βCD), which played a crucial role as electrostatic stabilizers, providing polymeric/polyol coatings around the magnetic cores. Methods: The composition, morphology, and magnetic properties of the nanospheres were analyzed using Transmission Electron and Atomic Force Microscopies (TEM, AFM), Nuclear Magnetic Resonance (NMR), X-ray Diffraction Diffractometry (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Matrix-Assisted Laser Desorption/Ionization (MALDI) and Vibrating Sample Magnetometry (VSM). Results: The obtained nanoparticles (@Fe3O4-PEGs and @Fe3O4-βCD) showed diameters between 90 and 250 nm, depending on the polymer used and the Fe3O4·6H2O precursor concentration, typically, 0.13 M at 200 °C and 24 h of reaction. MNPs exhibited superparamagnetism with high saturation mass magnetization at room temperature, reaching values of 59.9 emu/g (@Fe3O4-PEG6000), and no ferromagnetism. Likewise, they showed temperature elevation after applying an alternating magnetic field (AMF), obtaining Specific Absorption Rate (SAR) values of up to 51.87 ± 2.23 W/g for @Fe3O4-PEG6000. Additionally, the formed systems are susceptible to click chemistry, as was demonstrated in the case of the cannabidiol-propargyl derivative (CBD-Pro), which was synthesized and covalently attached to the azide functionalized surface of @Fe3O4-PEG400-N3. Prepared MNPs are highly dispersible in water, PBS, and citrate buffer, remaining in suspension for over 2 weeks, and non-toxic in the T84 human colon cancer cell line, Conclusions: indicating that they are ideal candidates for biomedical applications. Full article
(This article belongs to the Special Issue Recent Advances in Biomedical Applications of Magnetic Nanomaterials)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying article 51-100 on page 2 of 16.
Go to page     chevron_left 1 2 3 4 5 chevron_right last_page
Back to TopTop