Next Issue
Volume 16, December
Previous Issue
Volume 16, October
 
 

Pharmaceutics, Volume 16, Issue 11 (November 2024) – 140 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Cover Story (view full-size image):
Order results
Result details
Section
Select all
Export citation of selected articles as:
15 pages, 492 KiB  
Review
Recent Advances in Peptide Drug Discovery: Novel Strategies and Targeted Protein Degradation
by Katarina Vrbnjak and Raj Nayan Sewduth
Pharmaceutics 2024, 16(11), 1486; https://doi.org/10.3390/pharmaceutics16111486 - 20 Nov 2024
Viewed by 817
Abstract
Recent technological advancements, including computer-assisted drug discovery, gene-editing techniques, and high-throughput screening approaches, have greatly expanded the palette of methods for the discovery of peptides available to researchers. These emerging strategies, driven by recent advances in bioinformatics and multi-omics, have significantly improved the [...] Read more.
Recent technological advancements, including computer-assisted drug discovery, gene-editing techniques, and high-throughput screening approaches, have greatly expanded the palette of methods for the discovery of peptides available to researchers. These emerging strategies, driven by recent advances in bioinformatics and multi-omics, have significantly improved the efficiency of peptide drug discovery when compared with traditional in vitro and in vivo methods, cutting costs and improving their reliability. An added benefit of peptide-based drugs is the ability to precisely target protein–protein interactions, which are normally a particularly challenging aspect of drug discovery. Another recent breakthrough in this field is targeted protein degradation through proteolysis-targeting chimeras. These revolutionary compounds represent a noteworthy advancement over traditional small-molecule inhibitors due to their unique mechanism of action, which allows for the degradation of specific proteins with unprecedented specificity. The inclusion of a peptide as a protein-of-interest-targeting moiety allows for improved versatility and the possibility of targeting otherwise undruggable proteins. In this review, we discuss various novel wet-lab and computational multi-omic methods for peptide drug discovery, provide an overview of therapeutic agents discovered through these cutting-edge techniques, and discuss the potential for the therapeutic delivery of peptide-based drugs. Full article
Show Figures

Figure 1

19 pages, 6253 KiB  
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 743
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
Show Figures

Graphical abstract

15 pages, 4354 KiB  
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 404
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

25 pages, 9124 KiB  
Article
Enteric Delayed-Release Granules Loading Dendrobine Ameliorates Hyperlipidemia in Mice by Regulating Intestinal Flora Composition
by Shunqiang Song, Liangyu Yang, Tingting Chen and Yongai Xiong
Pharmaceutics 2024, 16(11), 1483; https://doi.org/10.3390/pharmaceutics16111483 - 20 Nov 2024
Viewed by 398
Abstract
Background/Objectives: In this paper, we created enteric delayed-release granules that load Dendrobine (DNL) directly into the intestinal flora of hyperlipidemic mice, based on the relationship between intestinal flora and hyperlipidemia. Methods: We then used pharmacodynamics and 16 Sr RNA high-throughput sequencing [...] Read more.
Background/Objectives: In this paper, we created enteric delayed-release granules that load Dendrobine (DNL) directly into the intestinal flora of hyperlipidemic mice, based on the relationship between intestinal flora and hyperlipidemia. Methods: We then used pharmacodynamics and 16 Sr RNA high-throughput sequencing to examine the hypolipidemic effects and mechanism of these granules. Solvent evaporation was used to create the DNL, which was then characterized using FT–IR, XRD, SEM, and DSC. A high-fat diet was used to create the mouse model of hyperlipidemia in C57BL/6J mice. Dendrobine, various dosages of DNL, TMAO, and the combination of TMAO and DNL were subsequently gavaged on the mice. The makeup of the intestinal flora in the mouse colon was analyzed using 16S rRNA sequencing, and the effectiveness and mechanism of DNL in controlling the intestinal flora for the treatment of hyperlipidemia in mice were investigated. Results/Conclusions: The findings showed that DNL could effectively improve the dysbiosis brought on by hyperlipidemia by significantly lowering the mice’s body weight and blood lipid level (p < 0.05), while also regulating the function of their intestinal flora, increasing the abundance of Actinobacteria (p < 0.05) and Thick-walled bacterium (p < 0.05), and decreasing the abundance of Desulfovibrio (p < 0.05) and Mycobacterium anisopliae (p < 0.05) in the intestinal flora of mice, inhibiting the growth of intestinal harmful microorganisms, providing space for the reproduction of beneficial bacteria, and thus maintaining the stability of the intestinal flora’s structure. Full article
Show Figures

Figure 1

27 pages, 11207 KiB  
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 407
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
Show Figures

Figure 1

14 pages, 3357 KiB  
Article
PRIMERS: Polydopamine Radioimmunotherapy with Image-Guided Monitoring and Enhanced Release System
by Shahinur Acter, Lindokuhle M. Ngema, Michele Moreau, Debarghya China, Akila Viswanathan, Kai Ding, Yahya E. Choonara, Sayeda Yasmin-Karim and Wilfred Ngwa
Pharmaceutics 2024, 16(11), 1481; https://doi.org/10.3390/pharmaceutics16111481 - 20 Nov 2024
Viewed by 622
Abstract
Background/Objectives: To overcome the side effects of conventional cancer treatment, multifunctional nanoparticles with image-guidance properties are increasingly desired to obtain enhanced therapeutic efficacy without any toxicity of the treatment. Herein, we introduce the potential of Polydopamine Radioimmunotherapy with Image-guided Monitoring and Enhanced (drug) [...] Read more.
Background/Objectives: To overcome the side effects of conventional cancer treatment, multifunctional nanoparticles with image-guidance properties are increasingly desired to obtain enhanced therapeutic efficacy without any toxicity of the treatment. Herein, we introduce the potential of Polydopamine Radioimmunotherapy with Image-guided Monitoring and Enhanced (drug) Release System (PRIMERS) to meet the challenges of currently used cancer therapy. Methods: The PDA nanobowls were synthesized using an emulsion-induced interfacial anisotropic assembly method followed by surface modification with high-Z material to obtained the final product PRIMERS. Results: The engineered multifunctional nanosystem “PRIMERS” could serve as fiducial markers with the potential for use in combination cancer therapy. By leveraging the advantages of the excellent surface functionalization capability of PDA, the anisotropic nanostructure (PDA nanobowls) has been successfully functionalized with gadolinium, which shows strong MRI contrast signal both in vitro in phantom and in vivo in animals. The results of anti-cancer drug loading and releasing efficiency of these functionalized nanobowls are presented. Moreover, the gadolinium-coated PDA nanobowls demonstrate the capacity for loading immunotherapy drugs (Anti-CD40) with activated release in acidic pH levels characteristic of the tumor microenvironment, with enhanced release following administration of radiation therapy in vitro. Conclusions: Overall, the results highlight the potential of this new technology for combining radiotherapy with activated image-guided drug delivery, which offers broad opportunities to overcome current challenges in cancer treatment. Full article
(This article belongs to the Special Issue Novel Strategies for Nanotherapeutics against Cancers)
Show Figures

Figure 1

9 pages, 3952 KiB  
Communication
Mechanical Characterization of Individual Needles in Microneedle Arrays: Factors Affecting Compression Test Results
by Yusuke Tsuboko, Hideyuki Sakoda, Yoshihiro Okamoto, Yusuke Nomura and Eiichi Yamamoto
Pharmaceutics 2024, 16(11), 1480; https://doi.org/10.3390/pharmaceutics16111480 - 20 Nov 2024
Viewed by 332
Abstract
Background: This study aims to investigate the impact of test conditions on the results of the compression testing of microneedle arrays (MNAs). Methods: Uniaxial compression tests were conducted on polyglycolic acid-fabricated biodegradable MNAs. Load–displacement curves were obtained for varying conditions, including the number [...] Read more.
Background: This study aims to investigate the impact of test conditions on the results of the compression testing of microneedle arrays (MNAs). Methods: Uniaxial compression tests were conducted on polyglycolic acid-fabricated biodegradable MNAs. Load–displacement curves were obtained for varying conditions, including the number of microneedles (MNs) compressed simultaneously, compression speeds, and compression angles. Subsequently, the buckling load and stiffness were calculated, and the MN deformation during compression was observed. Results: The buckling load and stiffness per MN decreased significantly with a simultaneous increase in compressed MNs. The mean buckling load and stiffness of 52 MNs in single-needle compression tests were 0.211 ± 0.008 N and 13.9 ± 1.3 N/mm, respectively, with no variation among the three MNAs. However, a significant difference in buckling load and stiffness was observed among the MNs within the MNAs. Additionally, buckling loads and stiffnesses were significantly lower in certain MNs at the same location in different MNAs. Buckling load and stiffness decreased significantly during inclined compression compared to during vertical compression. While the tests evaluate the mechanical properties of MNAs, test results may vary depending on test conditions. Conclusions: Compression testing of the individual MNs comprising an MNA helps evaluate the mechanical properties of MNs and ensure the quality of MNAs. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
Show Figures

Graphical abstract

21 pages, 968 KiB  
Review
Nanotechnology in Pain Management
by Andrew Torpey, Emily Bellow, Veronica Samojedny, Sukhpreet Ahluwalia, Amruta Desai, William Caldwell and Sergio Bergese
Pharmaceutics 2024, 16(11), 1479; https://doi.org/10.3390/pharmaceutics16111479 - 20 Nov 2024
Viewed by 556
Abstract
Chronic pain is a debilitating condition that affects millions of patients worldwide, contributing to a high disease burden and millions of dollars in lost wages, missed workdays, and healthcare costs. Opioids, NSAIDs, acetaminophen, gabapentinoids, muscle relaxants, anticonvulsants, and antidepressants are the most used [...] Read more.
Chronic pain is a debilitating condition that affects millions of patients worldwide, contributing to a high disease burden and millions of dollars in lost wages, missed workdays, and healthcare costs. Opioids, NSAIDs, acetaminophen, gabapentinoids, muscle relaxants, anticonvulsants, and antidepressants are the most used medications for chronic pain and carry significant side effects, including gastric bleeding, hepatotoxicity, stroke, kidney damage, constipation, dizziness, and arrhythmias. Opioids in particular carry the risk of long-term dependence, drug tolerance, and overdose. In 2022, 81,806 people died from opioid overdose in the United States alone. Alternative treatments for chronic pain are critically needed, and nanotechnology has emerged as a promising means of achieving effective long-term analgesia while avoiding the adverse side effects associated with conventional pharmacological agents. Nanotechnology-based treatments include liposomes, Poly Lactic-co-Glycolic Acid (PLGA) and other polymeric nanoparticles, and carbon-based polymers, which can help mitigate those adverse side effects. These nanomaterials can serve as drug delivery systems that facilitate controlled release and drug stability via the encapsulation of free molecules and protein-based drugs, leading to longer-lasting analgesia and minimizing side effects. In this review, we examine the role of nanotechnology in addressing concerns associated with conventional chronic pain treatments and discuss the ongoing efforts to develop novel, nanotechnology-based treatments for chronic pain such as nanocapacitor patches, gene therapy, the use of both viral and non-viral vectors, CRISPR, and scavengers. Full article
(This article belongs to the Special Issue Novel Therapeutic Approach to Inflammation and Pain)
Show Figures

Figure 1

2 pages, 154 KiB  
Correction
Correction: Jeong, J.-Y.; Hwang, Y.-J. Natural Phytochemical and Visible Light at Different Wavelengths Show Synergistic Antibacterial Activity against Staphylococcus aureus. Pharmaceutics 2024, 16, 612
by Jae-Young Jeong and You-Jin Hwang
Pharmaceutics 2024, 16(11), 1478; https://doi.org/10.3390/pharmaceutics16111478 - 20 Nov 2024
Viewed by 197
Abstract
In the original publication [...] Full article
19 pages, 3852 KiB  
Article
Antitubercular Activity of 7-Methyljuglone-Loaded Poly-(Lactide Co-Glycolide) Nanoparticles
by Bianca Diedericks, Anna-Mari Kok, Vusani Mandiwana, Bhavna Gowan Gordhan, Bavesh Davandra Kana, Suprakas Sinha Ray and Namrita Lall
Pharmaceutics 2024, 16(11), 1477; https://doi.org/10.3390/pharmaceutics16111477 - 20 Nov 2024
Viewed by 521
Abstract
Background/Objectives: Loading of natural products into poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as drug delivery systems for the treatment of diseases, such as tuberculosis (TB), has been widely explored. The current study investigated the use of PLGA nanoparticles with 7-methyljuglone (7-MJ), an active pure compound, [...] Read more.
Background/Objectives: Loading of natural products into poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as drug delivery systems for the treatment of diseases, such as tuberculosis (TB), has been widely explored. The current study investigated the use of PLGA nanoparticles with 7-methyljuglone (7-MJ), an active pure compound, isolated from the roots of Euclea natalensis A. DC. Methods: 7-MJ as well as its respective PLGA nanoparticles were tested for their antimycobacterial activity against Mycobacterium smegmatis (M. smegmatis), drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) (H37Rv), and multi-drug-resistant M. tuberculosis (MDR11). The cytotoxicity of 7-MJ as well as its respective PLGA nanoparticles were tested for their cytotoxic effect against differentiated human histiocytic lymphoma (U937) cells. Engulfment studies were also conducted to determine whether the PLGA nanoparticles are taken up by differentiated U937 cells. Results: 7-MJ has been shown to have a minimum inhibitory concentration (MIC) value of 1.6 µg/mL against M. smegmatis and multi-drug-resistant M. tuberculosis and 0.4 µg/mL against drug-susceptible M. tuberculosis. Whilst promising, 7-MJ was associated with cytotoxicity, with a fifty percent inhibition concentration (IC50) of 3.25 µg/mL on differentiated U937 cells. In order to lower the cytotoxic potential, 7-MJ was loaded into PLGA nanoparticles. The 7-MJ PLGA nanoparticles showed an 80-fold decrease in cytotoxic activity compared to free 7-MJ, and the loaded nanoparticles were successfully taken up by differentiated macrophage-like U937 cells. Conclusions: The results of this study suggested the possibility of improved delivery during TB therapy via the use of PLGA nanoparticles. Full article
Show Figures

Figure 1

29 pages, 2992 KiB  
Article
Silibinin-Loaded Liposomes: The Influence of Modifications on Physicochemical Characteristics, Stability, and Bioactivity Associated with Dermal Application
by Amjed Abdullah Karkad, Andrea Pirković, Milena Milošević, Bojan Stojadinović, Katarina Šavikin, Aleksandar Marinković and Aleksandra A. Jovanović
Pharmaceutics 2024, 16(11), 1476; https://doi.org/10.3390/pharmaceutics16111476 - 19 Nov 2024
Viewed by 356
Abstract
Background/Objectives: The aims of the presented study were the development of four types of silibinin-loaded liposomes (multilamellar liposomes—MLVs, sonicated small unilamellar liposomes—SUVs, UV-irradiated liposomes, and lyophilized liposomes) and their physicochemical characterization and biological potential related to skin health benefits. Methods: The characterization was [...] Read more.
Background/Objectives: The aims of the presented study were the development of four types of silibinin-loaded liposomes (multilamellar liposomes—MLVs, sonicated small unilamellar liposomes—SUVs, UV-irradiated liposomes, and lyophilized liposomes) and their physicochemical characterization and biological potential related to skin health benefits. Methods: The characterization was performed via the determination of the encapsulation efficiency (EE), particle size, polydispersity index, zeta potential, conductivity, mobility, storage stability, density, surface tension, viscosity, FT-IR, and Raman spectra. In addition, cytotoxicity on the keratinocytes and antioxidant and anti-inflammatory potential were also determined. Results: UV irradiation significantly changed the rheological and chemical properties of the liposomes and increased their cytotoxic effect. The lyophilization of the liposomes caused significant changes in their EE and physical characteristics, decreased their ABTS and DPPH radical scavenging potential, and increased their potential to reduce the expression of interleukin 1 beta (IL-1β) in cells treated with bacterial lipopolysaccharide. Sonication significantly changed the EE and physical and rheological properties of the liposomes, and slightly increased their cytotoxicity and reduction effect on IL-1β, while the anti-ABTS and anti-DPPH capacity of the liposomes significantly increased. All developed liposomes showed an increasing trend in particle size and a decreasing trend in zeta potential (absolute values) during storage. Conclusions: Silibinin-loaded liposomes (MLVs and lyophilized) showed promising antioxidant activity (toward reactive oxygen species generated in cells) and anti-inflammatory effects (reducing macrophage inhibitory factor expression) on keratinocytes and did not lead to a change in their viability. Future perspectives will focus on wound healing, anti-aging, and other potential of developed liposomes with silibinin in sophisticated cell-based models of skin diseases, wounds, and aging. Full article
(This article belongs to the Section Drug Targeting and Design)
Show Figures

Figure 1

47 pages, 3373 KiB  
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
Viewed by 836
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

22 pages, 5326 KiB  
Article
Improving the Theranostic Potential of Magnetic Nanoparticles by Coating with Natural Rubber Latex for Ultrasound, Photoacoustic Imaging, and Magnetic Hyperthermia: An In Vitro Study
by Thiago T. Vicente, Saeideh Arsalani, Mateus S. Quiel, Guilherme S. P. Fernandes, Keteryne R. da Silva, Sandra Y. Fukada, Alexandre J. Gualdi, Éder J. Guidelli, Oswaldo Baffa, Antônio A. O. Carneiro, Ana Paula Ramos and Theo Z. Pavan
Pharmaceutics 2024, 16(11), 1474; https://doi.org/10.3390/pharmaceutics16111474 - 19 Nov 2024
Viewed by 496
Abstract
Background/Objectives: Magnetic nanoparticles (MNPs) have gained attention in theranostics for their ability to combine diagnostic imaging and therapeutic capabilities in a single platform, enhancing targeted treatment and monitoring. Surface coatings are essential for stabilizing MNPs, improving biocompatibility, and preventing oxidation that could compromise [...] Read more.
Background/Objectives: Magnetic nanoparticles (MNPs) have gained attention in theranostics for their ability to combine diagnostic imaging and therapeutic capabilities in a single platform, enhancing targeted treatment and monitoring. Surface coatings are essential for stabilizing MNPs, improving biocompatibility, and preventing oxidation that could compromise their functionality. Natural rubber latex (NRL) offers a promising coating alternative due to its biocompatibility and stability-enhancing properties. While NRL-coated MNPs have shown potential in applications such as magnetic resonance imaging, their effectiveness in theranostics, particularly magnetic hyperthermia (MH) and photoacoustic imaging (PAI), remains underexplored. Methods: In this study, iron oxide nanoparticles were synthesized via coprecipitation, using NRL as the coating agent. The samples were labeled by NRL amount used during synthesis: NRL-100 for 100 μL and NRL-400 for 400 μL. Results: Characterization results showed that NRL-100 and NRL-400 samples exhibited improved stability with zeta potentials of −27 mV and −30 mV, respectively and higher saturation magnetization values of 79 emu/g and 88 emu/g of Fe3O4. Building on these findings, we evaluated the performance of these nanoparticles in biomedical applications, including magnetomotive ultrasound (MMUS), PAI, and MH. NRL-100 and NRL-400 samples showed greater displacements and higher contrast in MMUS than uncoated samples (5, 8, and 9 µm) at 0.5 wt%. In addition, NRL-coated samples demonstrated an improved signal-to-noise ratio (SNR) in PAI. SNR values were 24.72 (0.51), 31.44 (0.44), and 33.81 (0.46) dB for the phantoms containing uncoated MNPs, NRL-100, and NRL-400, respectively. Calorimetric measurements for MH confirmed the potential of NRL-coated MNPs as efficient heat-generating agents, showing values of 43 and 40 W/g for NRL-100 and NRL-400, respectively. Conclusions: Overall, NRL-coated MNPs showed great promise as contrast agents in MMUS and PAI imaging, as well as in MH applications. Full article
(This article belongs to the Special Issue Recent Advances in Biomedical Applications of Magnetic Nanomaterials)
Show Figures

Figure 1

15 pages, 2139 KiB  
Article
Evaluation of the Potential of Novel Co-Processed Excipients to Enable Direct Compression and Modified Release of Ibuprofen
by Ivana Aleksić, Teodora Glišić, Slobodanka Ćirin-Varađan, Mihal Djuris, Jelena Djuris and Jelena Parojčić
Pharmaceutics 2024, 16(11), 1473; https://doi.org/10.3390/pharmaceutics16111473 - 19 Nov 2024
Viewed by 467
Abstract
Background/Objectives: Improving the production rates of modern tablet presses places ever greater demands on the performance of excipients. Although co-processing has emerged as a promising solution, there is still a lack of directly compressible excipients for modified-release formulations. The aim of the [...] Read more.
Background/Objectives: Improving the production rates of modern tablet presses places ever greater demands on the performance of excipients. Although co-processing has emerged as a promising solution, there is still a lack of directly compressible excipients for modified-release formulations. The aim of the present study was to address this issue by investigating the potential of novel co-processed excipients for the manufacture of modified-release tablets containing ibuprofen. Methods: The excipients were prepared by melt granulation of lactose monohydrate with glyceryl palmitostearate as a binder. The influence of glyceryl palmitostearate particle size, ibuprofen content, compression pressure, and compression speed on the compaction behavior of the tablet blends was analyzed. Results: Novel co-processed excipients ensured good flowability and acceptable mechanical properties of the tablets containing up to 70% ibuprofen. Furthermore, lipid-based co-processed excipients proved to be very promising for directly compressible formulations with high-dose, highly adhesive active pharmaceutical ingredients such as ibuprofen, as they do not require additional lubricants. The influence of compression speed on the tensile strength of the tablets prepared was not pronounced, indicating the robustness of these directly compressible excipients. The investigated lipid-based excipients enabled a prolonged release of ibuprofen over 10 h. Conclusions: The novel lipid-based co-processed excipients have shown great potential for directly compressible formulations with modified release of high-dose, challenging active pharmaceutical ingredients. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Excipients Used in Solid Dosage Forms)
Show Figures

Figure 1

15 pages, 1799 KiB  
Article
Investigation of Antimicrobial and Anti-Inflammatory Efficacy of Newly Synthesized Pyrogallol-Coumarin Hybrids: In Vitro and In Silico Studies
by Dušica Simijonović, Edina Avdović, Sandra Jovičić Milić, Marko Antonijević, Dejan Milenković, Katarina Marković, Mirjana Grujović, Danijela Lj. Stojković, Milan Dekić and Zoran Marković
Pharmaceutics 2024, 16(11), 1472; https://doi.org/10.3390/pharmaceutics16111472 - 18 Nov 2024
Viewed by 442
Abstract
Background: The aim of this study is to present the synthesis of two new compounds with promising antimicrobial and anti-inflammatory properties using precursors that contain pyrogallol and coumarin units. Methods: The characterization of the obtained compounds (PCHs) (E)-N [...] Read more.
Background: The aim of this study is to present the synthesis of two new compounds with promising antimicrobial and anti-inflammatory properties using precursors that contain pyrogallol and coumarin units. Methods: The characterization of the obtained compounds (PCHs) (E)-N′-(1-(2,4-dioxochroman-3-ylidene)ethyl)-2,3,4-trihydroxybenzohydrazide (PCH-1) and (E)-N′-(1-(2,4-dioxochroman-3-ylidene)ethyl)-3,4,5-trihydroxybenzohydrazide (PCH-2) was performed using various spectroscopic methods in combination with the DFT methods. To evaluate antimicrobial and anti-inflammatory activities, PCHs were tested against 13 different types of microorganisms and soybean lipoxygenase. To determine the specific mechanisms of anti-LOX activity, molecular docking and molecular dynamics studies were performed. Results: These compounds had the most potent antibacterial activity against the bacterium Proteus mirabilis ATCC 12453, with a MIC value of 31.125 µg/mL. In addition, three standard bacterial species were chosen to evaluate the antibiofilm activity of tested substances. The results showed that the strongest effect of PCH-2 was noticed on the biofilm formation of Staphylococcus aureus ATCC 25923 (BIC50 at 378 µg/mL). The anti-LOX results indicate that PCHs have excellent activity with the IC50 value for PCH-1 = 38.12 μM and PCH-2 = 34.12 μM. Conclusions: The obtained in vitro and in silico results confirm the strong inhibitory potential of the investigated compounds. Full article
Show Figures

Figure 1

16 pages, 4552 KiB  
Article
Synthesis of Self-Assembled Nanostructured Cisplatin Using the RESS Process
by Sudhir Kumar Sharma, Loganathan Palanikumar, Renu Pasricha, Thirumurugan Prakasam, Mazin Magzoub and Ramesh Jagannathan
Pharmaceutics 2024, 16(11), 1471; https://doi.org/10.3390/pharmaceutics16111471 - 18 Nov 2024
Viewed by 483
Abstract
Background/Objectives: The primary goal of our research is to develop a process to prepare an aqueous dispersion of Cisplatin, an important anticancer drug, with increased solubility and storage stability. Method: In this context, we report the use of a customized RESS process for [...] Read more.
Background/Objectives: The primary goal of our research is to develop a process to prepare an aqueous dispersion of Cisplatin, an important anticancer drug, with increased solubility and storage stability. Method: In this context, we report the use of a customized RESS process for the synthesis of a novel, amber-colored and viscous aqueous cisplatin solution, an important anticancer drug, which we have denoted as “liquid” cisplatin. Results: Using specialized liquid cell in situ transmission electron microscopy (Liquid in situ TEM) and Raman spectroscopy, we demonstrated that “liquid” cisplatin comprises a bi-modal distribution of a highly solvated network of stable cisplatin nanoclusters in water and exhibited 27 times greater water solubility than standard cisplatin. More importantly, “liquid” cisplatin was stable at ambient conditions for over two years. Extensive analytical characterization of “liquid” cisplatin confirmed that it retained the original chemical identity of cisplatin. Cell viability and apoptosis studies on human lung adenocarcinoma A549 cells provided compelling evidence that “liquid” cisplatin demonstrated a more sustained anticancer effect compared to standard cisplatin. Conclusions: Aqueous cisplatin solubility was increased by 27X in the “liquid” cisplatin medium which retained its bio efficacy over a 2-year period. Our experimental results suggest the possibility of developing non-invasive and highly effective novel cisplatin drug-delivery platforms. Full article
(This article belongs to the Special Issue Supercritical Techniques for Pharmaceutical Applications)
Show Figures

Figure 1

24 pages, 1938 KiB  
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
Viewed by 528
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
Show Figures

Graphical abstract

17 pages, 5675 KiB  
Article
Antibacterial and Inhibitory Activity of Nora and Mepa Efflux Pumps of Estragole Complexed to β-Cyclodextrin (ES/β-CD) In Vitro Against Staphylococcus aureus Bacteria, Molecular Docking and MPO-Based Pharmacokinetics Prediction
by Roger Henrique Sousa da Costa, Renata Torres Pessoa, Eduardo dos Santos Silva, Isaac Moura Araujo, Sheila Alves Gonçalves, Janaína Esmeraldo Rocha, Francisco Nascimento Pereira Junior, Naiara Cipriano Oliveira, Victor Moreira de Oliveira, Matheus Nunes da Rocha, Emmanuel Silva Marinho, Natália Kelly Gomes de Carvalho, José Galberto Martins da Costa, Hélcio Silva dos Santos and Irwin Rose Alencar de Menezes
Pharmaceutics 2024, 16(11), 1469; https://doi.org/10.3390/pharmaceutics16111469 - 18 Nov 2024
Viewed by 521
Abstract
Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from [...] Read more.
Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from the cell. Methodology: Several compounds and antibiotics, such as ciprofloxacin and norfloxacin, were used to evaluate the antimicrobial activity and the ability of the ES/β-CD complex to reverse resistance. Methods: The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. Results: The ES/β-CD complex did not show significant direct antibacterial activity. However, it modulated the action of norfloxacin, decreasing the MIC when combined with this antibiotic in the 1199B (NorA) strain. These results suggest a potential for synergy but not a direct inhibition of efflux pumps. Conclusion: ES/β-CD can potentiate the efficacy of some antibiotics but does not directly act as an efflux pump inhibitor; it is more of an antibiotic potentiator than a direct solution to bacterial resistance. The molecular docking simulation data suggest its high affinity for forming the ES/β-CD complex. The pharmacokinetic predictions based on MPO suggest that the compound has moderate lipophilicity, highly effective cellular permeability, and low incidence of organic toxicity, pointing to a promising pharmacological principle with controlled daily oral dosing. Conclusions: These results indicate this complex’s possible and relevant association as an adjuvant in antibiotic therapy to reduce multidrug-resistant bacteria; however, new in vivo assays are necessary to confirm this effect. Full article
Show Figures

Figure 1

28 pages, 2973 KiB  
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
Viewed by 819
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

20 pages, 3601 KiB  
Article
Formulation, Characterisation, and Biocompatibility Assessment of Rifampicin-Loaded Poly(d,l-lactide-co-glycolide) Composites for Local Treatment of Orthopaedic and Wound Infections
by Mitali Singhal, Colin C. Seaton, Alexander Surtees and Maria G. Katsikogianni
Pharmaceutics 2024, 16(11), 1467; https://doi.org/10.3390/pharmaceutics16111467 - 18 Nov 2024
Viewed by 881
Abstract
Background/Objectives: The escalating challenge of antimicrobial resistance (AMR) necessitates the development of targeted antibiotic delivery platforms, minimising systemic administration. Polymer-based drug delivery emerges as a promising solution, ensuring sustained release and prolonged efficacy of bioactive compounds, ensuring long-term efficacy. Methods: This study focuses [...] Read more.
Background/Objectives: The escalating challenge of antimicrobial resistance (AMR) necessitates the development of targeted antibiotic delivery platforms, minimising systemic administration. Polymer-based drug delivery emerges as a promising solution, ensuring sustained release and prolonged efficacy of bioactive compounds, ensuring long-term efficacy. Methods: This study focuses on encapsulating rifampicin (RIF), a key antibiotic for orthopaedic and wound-related infections, within Poly(d,l-lactide-co-glycolide) (PLGA), a biodegradable polymer, through solvent casting, to formulate a PLGA-RIF composite membrane. Comprehensive characterisation, employing Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermal analysis and X-ray Diffraction (XRD), confirmed the integrity of both the starting and produced materials. UV-Vis spectroscopy revealed a controlled drug release profile over 21 days in various media, with the chosen media influencing the drug release, notably the tryptic soya broth (TSB) caused the highest release. The quantitative assessment of the antimicrobial efficacy of the developed PLGA-RIF composite was conducted by measuring the size of the inhibition zones against both Gram-negative and Gram-positive bacteria. Results: The results confirmed the composite’s potential as a robust antibacterial biomaterial, demonstrating a rapid and effective antibacterial response. Cytocompatibility tests incorporated human fibroblast and osteoblast-like cell lines and demonstrated that the RIF:PLGA (1:8) formulation maintained eukaryotic cell viability, indicating the composite’s potential for targeted medical applications in combating bacterial infections with minimal systemic impact. Conclusions: This study presents the significance of investigating drug release within appropriate and relevant physiological media. A key novelty of this work therefore lies in the exploration of drug release dynamics across different media, allowing for a comprehensive understanding of how varying physiological conditions may influence drug release and its effect on biological responses. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release, 2nd Edition)
Show Figures

Figure 1

29 pages, 7806 KiB  
Article
Formulation and Ex Vivo Evaluation of Ivermectin Within Different Nano-Drug Delivery Vehicles for Transdermal Drug Delivery
by Eunice Maureen Steenekamp, Wilna Liebenberg, Hendrik J. R. Lemmer and Minja Gerber
Pharmaceutics 2024, 16(11), 1466; https://doi.org/10.3390/pharmaceutics16111466 - 18 Nov 2024
Viewed by 910
Abstract
Background/Objectives: Ivermectin gained widespread attention as the “miracle drug” during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. [...] Read more.
Background/Objectives: Ivermectin gained widespread attention as the “miracle drug” during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. Since the late 2000s, this bio-inspired active pharmaceutical ingredient (API) gained renewed interest for its diverse therapeutic capabilities. However, producing ivermectin formulations does remain challenging due to its poor water solubility, resulting in low bioavailability after oral administration. Therefore, the transdermal drug delivery of ivermectin was considered to overcome these challenges, which are observed after oral administration. Methods: Ivermectin was incorporated in a nano-emulsion, nano-emulgel and a colloidal suspension as ivermectin-loaded nanoparticles. The nano-drug delivery vehicles were optimized, characterized and evaluated through in vitro membrane release studies, ex vivo skin diffusion studies and tape-stripping to determine whether ivermectin was successfully released from its vehicle and delivered transdermally and/or topically throughout the skin. This study concluded with cytotoxicity tests using the methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on both human immortalized epidermal keratinocytes (HaCaT) and human immortalized dermal fibroblasts (BJ-5ta). Results: Ivermectin was successfully released from each vehicle, delivered transdermally and topically throughout the skin and demonstrated little to no cytotoxicity at concentrations that diffused through the skin. Conclusions: The type of nano-drug delivery vehicle used to incorporate ivermectin influences its delivery both topically and transdermally, highlighting the dynamic equilibrium between the vehicle, the API and the skin. Full article
(This article belongs to the Special Issue Transdermal Delivery: Challenges and Opportunities)
Show Figures

Figure 1

18 pages, 4455 KiB  
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
Viewed by 666
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 KiB  
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
Viewed by 882
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

14 pages, 1197 KiB  
Article
Pharmacokinetics and Quantitative Structure–Pharmacokinetics Relationship Study of Xanthine Derivatives with Antidepressant, Anti-Inflammatory, and Analgesic Activity in Rats
by Artur Świerczek, Małgorzata Szafarz, Agnieszka Cios, Jan Kobierski, Krzysztof Pociecha, Daniel Attard Saliba, Grażyna Chłoń-Rzepa and Elżbieta Wyska
Pharmaceutics 2024, 16(11), 1463; https://doi.org/10.3390/pharmaceutics16111463 - 16 Nov 2024
Viewed by 472
Abstract
Objective: The aim of this study was to develop quantitative structure–pharmacokinetics relationship (QSPKR) models for a group of xanthine derivatives with proven pharmacological activity and to investigate its applicability for the prediction of the pharmacokinetics of these compounds. Methods: The SYBYL-X, KowWin, and [...] Read more.
Objective: The aim of this study was to develop quantitative structure–pharmacokinetics relationship (QSPKR) models for a group of xanthine derivatives with proven pharmacological activity and to investigate its applicability for the prediction of the pharmacokinetics of these compounds. Methods: The SYBYL-X, KowWin, and MarvinSketch programs were employed to generate a total of fourteen descriptor variables for a series of new compounds: 7- and 7,8-substituted theophylline derivatives (GR-1–GR-8) and three well-known methylxanthines. Pharmacokinetic profiles of all compounds were determined after intravenous administration of studied compounds to cannulated male rats. Pharmacokinetic parameters were calculated using noncompartmental analysis. Results: Multiple linear regression revealed that logD was the main determinant of the variability in Vss, λz, and CL of the studied compounds. Moreover, λz and CL depended on LUMO and HEFO, while for Vz COAR was the only explanatory variable. The developed QSPKR models accounted for most of the variation in Vss, λz, CL, and fraction unbound (fu) (R2 ranged from 0.68 to 0.91). Cross-validation confirmed the predictive ability of the models (Q2 = 0.60, 0.71, 0.34, and 0.32 for Vss, λz, CL, and fu, respectively). Conclusions: The multivariate QSPKR models developed in this study adequately predicted the overall pharmacokinetic behavior of xanthine derivatives in rats. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
Show Figures

Figure 1

12 pages, 2136 KiB  
Article
Development of a Water-Soluble Nanomicellar Formulation Loaded with Trans-Resveratrol Using Polyethylene Glycol Monostearate for the Treatment of Intracerebral Hemorrhage
by Kengo Banshoya, Aoi Machida, Saki Kawamura, Tetsuhiro Yamada, Riko Okada, Yui Kawamoto, Hikaru Kimura, Sachi Shibata, Yuhzo Hieda, Yoshiharu Kaneo, Tetsuro Tanaka and Masatoshi Ohnishi
Pharmaceutics 2024, 16(11), 1462; https://doi.org/10.3390/pharmaceutics16111462 - 15 Nov 2024
Viewed by 484
Abstract
Background/Objectives: Trans-resveratrol (Res) has been reported to possess many biological activities, including neuroprotective effects, owing to its anti-inflammatory and antioxidant properties. However, Res has very low water solubility, which limits its therapeutic application. In this work, we formulated water-soluble micellar formulations incorporating Res [...] Read more.
Background/Objectives: Trans-resveratrol (Res) has been reported to possess many biological activities, including neuroprotective effects, owing to its anti-inflammatory and antioxidant properties. However, Res has very low water solubility, which limits its therapeutic application. In this work, we formulated water-soluble micellar formulations incorporating Res using polyethylene glycol monostearate (stPEG). Methods: These formulations (stPEG/Res) were developed using five types of stPEG containing 10, 25, 40, 55 and 140 PEG repeat units. The formulations were characterized for Res content, water solubility, particle size, zeta potential, precipitation, biodistribution, and efficacy against neuronal and motor dysfunction in intracerebral hemorrhage (ICH). Results: Intravenous administration of stPEG40/Res, which demonstrated particle size, water solubility, and biodistribution properties suitable for intravenous administration, suppressed neurological and motor dysfunction following in a collagenase-induced ICH mouse model. These effects were inhibited by zinc protoporphyrin-9, an inhibitor of the antioxidant enzyme heme oxygenase-1, suggesting that Res contributes to antioxidant enzyme expression and anti-inflammatory activity. Conclusions: The stPEG/Res micellar formulation developed in this study may offer a promising therapeutic approach for ICH treatment. Full article
(This article belongs to the Special Issue Nanoparticle-Mediated Targeted Drug Delivery Systems)
Show Figures

Figure 1

18 pages, 4537 KiB  
Review
Quantitative Approach to Explore Regulatory T Cell Activity in Immuno-Oncology
by Alejandro Serrano, Sara Zalba, Juan Jose Lasarte, Iñaki F. Troconiz, Natalia Riva and Maria J. Garrido
Pharmaceutics 2024, 16(11), 1461; https://doi.org/10.3390/pharmaceutics16111461 - 15 Nov 2024
Viewed by 512
Abstract
The failure of immunotherapies in cancer patients is being widely studied due to the complexities present in the tumor microenvironment (TME), where regulatory T cells (Treg) appear to actively participate in providing an immune escape mechanism for tumors. Therefore, therapies to specifically inhibit [...] Read more.
The failure of immunotherapies in cancer patients is being widely studied due to the complexities present in the tumor microenvironment (TME), where regulatory T cells (Treg) appear to actively participate in providing an immune escape mechanism for tumors. Therefore, therapies to specifically inhibit tumor-infiltrating Treg represent a challenge, because Treg are distributed throughout the body and provide physiological immune homeostasis to prevent autoimmune diseases. Characterization of immunological and functional profiles could help to identify the mechanisms that need to be inhibited or activated to ensure Treg modulation in the tumor. To address this, quantitative in silico approaches based on mechanistic mathematical models integrating multi-scale information from immune and tumor cells and the effect of different therapies have allowed the building of computational frameworks to simulate different hypotheses, some of which have subsequently been experimentally validated. Therefore, this review presents a list of diverse computational mathematical models that examine the role of Treg as a crucial immune resistance mechanism contributing to the failure of immunotherapy. In addition, this review highlights the relevance of certain molecules expressed in Treg that are associated with the TME immunosuppression, which could be incorporated into the mathematical model for a better understanding of the contribution of Treg modulation. Finally, different preclinical and clinical combinations of molecules are also included to show the trend of new therapies targeting Treg. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
Show Figures

Graphical abstract

21 pages, 9370 KiB  
Article
Thymoquinone Pectin Beads Produced via Electrospray: Enhancing Oral Targeted Delivery for Colorectal Cancer Therapy
by Mulham Alfatama, Hazem Choukaife, Okba Al Rahal and Nur Zahirah Mohamad Zin
Pharmaceutics 2024, 16(11), 1460; https://doi.org/10.3390/pharmaceutics16111460 - 15 Nov 2024
Viewed by 552
Abstract
Background/Objectives: Thymoquinone (TQ) exhibits diverse biological activities, but its poor solubility and bioavailability limit its cancer efficacy, requiring innovative solutions. This study explores the development of an oral delivery system targeting colon cancer based on TQ pectin beads (TQ-PBs) produced through an [...] Read more.
Background/Objectives: Thymoquinone (TQ) exhibits diverse biological activities, but its poor solubility and bioavailability limit its cancer efficacy, requiring innovative solutions. This study explores the development of an oral delivery system targeting colon cancer based on TQ pectin beads (TQ-PBs) produced through an adjustable electrospray technique. This study hypothesised that adjusting bead diameter through the electrospray technique enables precise control over water absorption and erosion rates, thereby achieving a controlled release profile for encapsulated TQ, which enhances targeted delivery to the colon. Methods: TQ-PBs were synthesised and optimised using an electrospray technique based on the ionic gelation method. The prepared beads were characterised based on particle size, sphericity, encapsulation efficiency (EE), water uptake, erosion, surface morphology, molecular interactions, and texture. The cumulative TQ release studies, an accelerated stability test, and cytotoxicity evaluation against the colon cancer HT-29 cell line were also assessed. Results: The optimised TQ-PB formulation demonstrated an average bead size of 2.05 ± 0.14 mm, a sphericity of 0.96 ± 0.05, and an EE of 90.32 ± 1.04%. The water uptake was 287.55 ± 10.14% in simulated gastric fluid (SGF), 462.15 ± 12.73% in simulated intestinal fluid (SIF), and 772.41 ± 13.03% in simulated colonic fluid (SCF), with an erosion rate of 45.23 ± 5.22%. TQ release was minimal in SGF (8.13 ± 1.94% after 2 h), controlled in SIF (29.35 ± 3.65% after 4 h), and accelerated in SCF (94.43 ± 2.4% after 3 h). Stability studies over one month showed a size reduction of 17.50% and a 6.59% decrease in TQ content. Cytotoxicity assessments revealed significant anticancer activity of TQ-PB, with an IC50 of 80.59 ± 2.2 μg/mL. Conclusions: These findings underscore the potential of TQ-PB as an effective oral drug delivery system for targeted colorectal cancer therapy. Full article
Show Figures

Graphical abstract

12 pages, 1659 KiB  
Article
Comparative Pharmacokinetic Assessment of Curcumin in Rats Following Intratracheal Instillation Versus Oral Administration: Concurrent Detection of Curcumin and Its Conjugates in Plasma by LC-MS/MS
by Nan Li, Jinle Lou, Lingchao Wang, Wenpeng Zhang, Chunmei Jin and Xiaomei Zhuang
Pharmaceutics 2024, 16(11), 1459; https://doi.org/10.3390/pharmaceutics16111459 - 15 Nov 2024
Viewed by 373
Abstract
Objective: To establish and validate an LC-MS/MS method for the simultaneous determination of curcumin (CUR) as well as its glucuronide conjugate (COG) and sulfate conjugate (COS) in rat plasma. The method was employed to evaluate and compare the pharmacokinetic behaviors of curcumin following [...] Read more.
Objective: To establish and validate an LC-MS/MS method for the simultaneous determination of curcumin (CUR) as well as its glucuronide conjugate (COG) and sulfate conjugate (COS) in rat plasma. The method was employed to evaluate and compare the pharmacokinetic behaviors of curcumin following oral and intratracheal administration in rats. Methods: Rat plasma samples were separated by chromatography on a C18 column after protein precipitation with acetonitrile. Gradient elution with a mobile phase of 0.5 mM ammonium acetate in acetonitrile was utilized. Mass spectrometry detection incorporated an electrospray ionization (ESI) source, multiple reaction monitoring (MRM), and dual-mode (positive and negative) scanning for quantitative analysis. A total of 12 SD rats were randomly divided into two groups and were orally (20 mg/kg) or intratracheally (10 mg/kg) administrated curcumin, respectively. CUR, COG, and COS concentrations in plasma were measured to assess pharmacokinetic disparities. Results: The method demonstrated linearity within the ranges of 2–400 ng/mL for CUR and COS and 5–1000 ng/mL for COG. Intratracheal administration significantly elevated CUR plasma concentrations compared to oral administration. The exposure of COG was higher than COS following oral administration. Conversely, intratracheal administration resulted in markedly higher COS exposure, with no significant difference in COG exposure after dose normalization between oral and inhalation routes. Conclusions: The established LC-MS/MS method provides a reliable tool for the simultaneous measurement of CUR, COG, and COS in rat plasma, facilitating preclinical pharmacokinetic investigations. The study reveals distinct pharmacokinetic profiles for CUR following oral versus intratracheal administration, suggesting that inhalation may offer superior therapeutic efficacy. Full article
(This article belongs to the Special Issue ADME Properties in the Drug Delivery)
Show Figures

Figure 1

18 pages, 1230 KiB  
Review
Optimization Processes of Clinical Chelation-Based Radiopharmaceuticals for Pathway-Directed Targeted Radionuclide Therapy in Oncology
by Katsumi Tomiyoshi, Lydia J. Wilson, Firas Mourtada, Jennifer Sims Mourtada, Yuta Namiki, Wataru Kamata, David J. Yang and Tomio Inoue
Pharmaceutics 2024, 16(11), 1458; https://doi.org/10.3390/pharmaceutics16111458 - 15 Nov 2024
Viewed by 615
Abstract
Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and [...] Read more.
Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT, 68Ga and 99mTc are the current standards for diagnostic radionuclides, while 177Lu and 225Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to 225Ac daughters 221Fr and 213Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose–response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses. Full article
Show Figures

Graphical abstract

14 pages, 3108 KiB  
Article
Evaluation of Platonia insignis Mart. (Bacuri Butter) and Biopolymers from the Puree of Allium cepa L. (Yellow Onion Bulb) for Wound Healing in Horses
by André M. Resende, Beatriz A. Miranda, Luiza B. Silva, Andressa B. Oliveira, Márcio B. Castro, Isabel L. Macêdo, Bruno S. L. Dallago, Hernane S. Barud, Marco A. Costa Borges, Clovis A. Ribeiro, Diogenes S. Dias and Rita C. Campebell
Pharmaceutics 2024, 16(11), 1457; https://doi.org/10.3390/pharmaceutics16111457 - 15 Nov 2024
Viewed by 416
Abstract
Background/Objectives: Skin injuries are common in the equine clinical practice, requiring effective treatment to support natural healing. Bacuri butter is gaining attention for its potential in wound healing and its anti-inflammatory, antimicrobial, and antioxidant properties. Natural polymers such as onion (Allium cepa [...] Read more.
Background/Objectives: Skin injuries are common in the equine clinical practice, requiring effective treatment to support natural healing. Bacuri butter is gaining attention for its potential in wound healing and its anti-inflammatory, antimicrobial, and antioxidant properties. Natural polymers such as onion (Allium cepa) bioplastics have been investigated for their potential as occlusive dressings and for tissue regeneration. Methods: This study evaluated the healing process of experimentally induced skin wounds on horses treated with bacuri butter, washed onion film, and unwashed onion film. Clinical and histopathological analyses of the wounds were conducted in six clinically healthy horses over 28 days, with a control group receiving Ringer’s lactate solution. The onion films were produced and characterized for their chemical structure and properties, while the bacuri butter was sourced and prepared for application. Results: All treatments, including the control group, promoted wound healing without relevant differences in wound contraction rates, gross aspect, or histopathological parameters. Conclusions: Therefore, despite minor variations observed in the clinical evaluations between the treatment groups, the bacuri butter or onion biopolymer showed no significant healing effect on skin wounds in horses. Additionally, this study showed the potential of equine models in testing novel therapeutic approaches for wound healing, benefiting both veterinary and human medicine. Full article
(This article belongs to the Special Issue Prospects of Hydrogels in Wound Healing)
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop