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Pharmaceutics, Volume 16, Issue 6 (June 2024) – 122 articles

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13 pages, 2988 KiB  
Article
Novel Hydrogels Based on the Nano-Emulsion Formulation Process: Development, Rheological Characterization, and Study as a Drug Delivery System
by Usama Jamshaid, Nicolas Anton, Mohamed Elhassan, Guillaume Conzatti and Thierry F. Vandamme
Pharmaceutics 2024, 16(6), 812; https://doi.org/10.3390/pharmaceutics16060812 - 14 Jun 2024
Viewed by 139
Abstract
In this study, we present a new type of polymer-free hydrogel made only from nonionic surfactants, oil, and water. Such a system is produced by taking advantage of the physicochemical behavior and interactions between nonionic surfactants and oil and water phases, according to [...] Read more.
In this study, we present a new type of polymer-free hydrogel made only from nonionic surfactants, oil, and water. Such a system is produced by taking advantage of the physicochemical behavior and interactions between nonionic surfactants and oil and water phases, according to a process close to spontaneous emulsification used in the production of nano-emulsions. Contrary to the classical process of emulsion-based gel formulation, we propose a simple one-step approach. Beyond the originality of the concept, these nanoemulgels appear as very promising systems able to encapsulate and deliver various molecules with different solubilities. In the first section, we propose a comprehensive investigation of the gel formation process and its limits through oscillatory rheological characterization, characterization of the sol/gel transitions, and gel strength. The second section is focused on the follow-up of the release of an encapsulated model hydrophilic molecule and on the impact of the rheological gel properties on the release profiles. Full article
17 pages, 1118 KiB  
Review
Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions
by Anne K. Ellis, Thomas B. Casale, Michael Kaliner, John Oppenheimer, Jonathan M. Spergel, David M. Fleischer, David Bernstein, Carlos A. Camargo, Jr., Richard Lowenthal and Sarina Tanimoto
Pharmaceutics 2024, 16(6), 811; https://doi.org/10.3390/pharmaceutics16060811 - 14 Jun 2024
Viewed by 154
Abstract
Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of [...] Read more.
Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy’s development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffyconfirm the activation of α and β adrenergic receptors, which are the key components of epinephrine’s mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis. Full article
16 pages, 4622 KiB  
Article
The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection
by J. Francis Borgio, Noor B. Almandil, Prathas Selvaraj, J. Sherlin John, Rahaf Alquwaie, Eman AlHasani, Norah F. Alhur, Razan Aldahhan, Reem AlJindan, Dana Almohazey, Sarah Almofty, T. Stalin Dhas and Sayed AbdulAzeez
Pharmaceutics 2024, 16(6), 810; https://doi.org/10.3390/pharmaceutics16060810 - 14 Jun 2024
Viewed by 206
Abstract
Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti- [...] Read more.
Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti-C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase–dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti-auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris, and significant (p-value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti-C. auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection. Full article
(This article belongs to the Special Issue Novel Drugs, Targets and Therapies against Infectious Diseases)
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18 pages, 6204 KiB  
Review
Advances in 2,3-Dimethylmaleic Anhydride (DMMA)-Modified Nanocarriers in Drug Delivery Systems
by Dong Wan, Yanan Wu, Yujun Liu, Yonghui Liu and Jie Pan
Pharmaceutics 2024, 16(6), 809; https://doi.org/10.3390/pharmaceutics16060809 - 14 Jun 2024
Viewed by 209
Abstract
Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers [...] Read more.
Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy. Full article
(This article belongs to the Special Issue Polymeric Micelles for Drug Delivery and Cancer Therapy)
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15 pages, 6889 KiB  
Article
The Controlled Preparation of a Carrier-Free Nanoparticulate Formulation Composed of Curcumin and Piperine Using High-Gravity Technology
by Ning Han, Yue Liu, Xin Liu, Pengyue Li, Yang Lu, Shouying Du and Kai Wu
Pharmaceutics 2024, 16(6), 808; https://doi.org/10.3390/pharmaceutics16060808 - 14 Jun 2024
Viewed by 168
Abstract
Carrier-free nanoparticulate formulations are an advantageous platform for the oral administration of insoluble drugs with the expectation of improving their bioavailability. However, the key limitation of exploiting carrier-free nanoparticulate formulations is the controlled preparation of drug nanoparticles on the basis of rational prescription [...] Read more.
Carrier-free nanoparticulate formulations are an advantageous platform for the oral administration of insoluble drugs with the expectation of improving their bioavailability. However, the key limitation of exploiting carrier-free nanoparticulate formulations is the controlled preparation of drug nanoparticles on the basis of rational prescription design. In the following study, we used curcumin (Cur) and piperine (Pip) as model water-insoluble drugs and developed a new method for the controlled preparation of carrier-free drug nanoparticles via multidrug co-assembly in a high-gravity environment. Encouraged by the controlled regulation of the nucleation and crystal growth rate of high-gravity technology accomplished by a rotating packed bed, co-amorphous Cur-Pip co-assembled multidrug nanoparticles with a uniform particle size of 130 nm were successfully prepared, exhibiting significantly enhanced dissolution performance and in vitro cytotoxicity. Moreover, the hydrogen bonding interactions between Cur and Pip in nanoparticles provide them with excellent re-dispersibility and storage stability. Moreover, the oral bioavailability of Cur was dramatically enhanced as a result of the smaller particle size of the co-assembled nanoparticles and the effective metabolic inhibitory effect of Pip. The present study provides a controlled approach to preparing a carrier-free nanoparticulate formulation through a multidrug co-assembly process in the high-gravity field to improve the oral bioavailability of insoluble drugs. Full article
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
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54 pages, 4234 KiB  
Review
Lipid Biomimetic Models as Simple Yet Complex Tools to Predict Skin Permeation and Drug–Membrane Biophysical Interactions
by Eduarda Fernandes, Carla M. Lopes and Marlene Lúcio
Pharmaceutics 2024, 16(6), 807; https://doi.org/10.3390/pharmaceutics16060807 - 14 Jun 2024
Viewed by 172
Abstract
The barrier function of the skin is primarily determined by its outermost layer, the Stratum Corneum (SC). The SC consists of corneocytes embedded in a lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids in equimolar proportions and is organised in [...] Read more.
The barrier function of the skin is primarily determined by its outermost layer, the Stratum Corneum (SC). The SC consists of corneocytes embedded in a lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids in equimolar proportions and is organised in a complex lamellar structure with different periodicities and lateral packings. This matrix provides a diffusion pathway across the SC for bioactive compounds that are administered to the skin. In this regard, and as the skin administration route has grown in popularity, there has been an increase in the use of lipid mixtures that closely resemble the SC lipid matrix, either for a deeper biophysical understanding or for pharmaceutical and cosmetic purposes. This review focuses on a systematic analysis of the main outcomes of using lipid mixtures as SC lipid matrix models for pharmaceutical and cosmetic purposes. Thus, a methodical evaluation of the main outcomes based on the SC structure is performed, as well as the main recent developments in finding suitable new in vitro tools for permeation testing based on lipid models. Full article
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18 pages, 1842 KiB  
Review
Prospect of Gold Nanoparticles in Pancreatic Cancer
by Tianyi Yin, Jingrun Han, Yuying Cui, Dong Shang and Hong Xiang
Pharmaceutics 2024, 16(6), 806; https://doi.org/10.3390/pharmaceutics16060806 - 14 Jun 2024
Viewed by 177
Abstract
Pancreatic cancer (PC) is characterized by its notably poor prognosis and high mortality rate, underscoring the critical need for advancements in its diagnosis and therapy. Gold nanoparticles (AuNPs), with their distinctive physicochemical characteristics, demonstrate significant application potential in cancer therapy. For example, upon [...] Read more.
Pancreatic cancer (PC) is characterized by its notably poor prognosis and high mortality rate, underscoring the critical need for advancements in its diagnosis and therapy. Gold nanoparticles (AuNPs), with their distinctive physicochemical characteristics, demonstrate significant application potential in cancer therapy. For example, upon exposure to lasers of certain wavelengths, they facilitate localized heating, rendering them extremely effective in photothermal therapy. Additionally, their extensive surface area enables the conjugation of therapeutic agents or targeting molecules, increasing the accuracy of drug delivery systems. Moreover, AuNPs can serve as radiosensitizers, enhancing the efficacy of radiotherapy by boosting the radiation absorption in tumor cells. Here, we systematically reviewed the application and future directions of AuNPs in the diagnosis and treatment of PC. Although AuNPs have advantages in improving diagnostic and therapeutic efficacy, as well as minimizing damage to normal tissues, concerns about their potential toxicity and safety need to be comprehensively evaluated. Full article
(This article belongs to the Topic Recent Advances in Anticancer Strategies)
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17 pages, 4395 KiB  
Article
In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia
by Ailing Wu, Houyin Shi, Luhan Yang, Hao Zhang, Xichen Nan, Dan Zhang, Zhuo Zhang, Chun Zhang, Siwei Chen, Xiujuan Fu, Lilan Ou, Lulu Wang, Yanyan Shi and Hao Liu
Pharmaceutics 2024, 16(6), 805; https://doi.org/10.3390/pharmaceutics16060805 - 14 Jun 2024
Viewed by 139
Abstract
Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central [...] Read more.
Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia. Full article
(This article belongs to the Special Issue Advances in Liposomes for Drug Delivery)
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17 pages, 2761 KiB  
Review
Development, Optimization, and Clinical Relevance of Lactoferrin Delivery Systems: A Focus on Ocular Delivery
by Erika Ponzini, Gloria Astolfi, Rita Grandori, Silvia Tavazzi and Piera Versura
Pharmaceutics 2024, 16(6), 804; https://doi.org/10.3390/pharmaceutics16060804 - 14 Jun 2024
Viewed by 194
Abstract
Lactoferrin (Lf), a multifunctional protein found abundantly in secretions, including tears, plays a crucial role in ocular health through its antimicrobial, immunoregulatory, anti-inflammatory, and antioxidant activities. Advanced delivery systems are desirable to fully leverage its therapeutic potential in treating ocular diseases. The process [...] Read more.
Lactoferrin (Lf), a multifunctional protein found abundantly in secretions, including tears, plays a crucial role in ocular health through its antimicrobial, immunoregulatory, anti-inflammatory, and antioxidant activities. Advanced delivery systems are desirable to fully leverage its therapeutic potential in treating ocular diseases. The process of Lf quantification for diagnostic purposes underscores the importance of developing reliable, cost-effective detection methods, ranging from conventional techniques to advanced nano-based sensors. Despite the ease and non-invasiveness of topical administration for ocular surface diseases, challenges such as rapid drug elimination necessitate innovations, such as Lf-loaded contact lenses and biodegradable polymeric nanocapsules, to enhance drug stability and bioavailability. Furthermore, overcoming ocular barriers for the treatment of posterior segment disease calls for nano-formulations. The scope of this review is to underline the advancements in nanotechnology-based Lf delivery methods, emphasizing the pivotal role of multidisciplinary approaches and cross-field strategies in improving ocular drug delivery and achieving better therapeutic outcomes for a wide spectrum of eye conditions. Full article
(This article belongs to the Special Issue Application Progress of Lactoferrin in Biomedicine)
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20 pages, 4629 KiB  
Review
Recent Progress of Multifunctional Molecular Probes for Triple-Negative Breast Cancer Theranostics
by Deyi Zhao, Zhe Li, Ding-Kun Ji and Qian Xia
Pharmaceutics 2024, 16(6), 803; https://doi.org/10.3390/pharmaceutics16060803 - 14 Jun 2024
Viewed by 209
Abstract
Breast cancer (BC) poses a significant threat to women’s health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive subtypes due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [...] Read more.
Breast cancer (BC) poses a significant threat to women’s health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive subtypes due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Traditional TNBC treatments often encounter issues such as low drug efficiency, limited tumor enrichment, and substantial side effects. Therefore, it is crucial to explore novel diagnostic and treatment systems for TNBC. Multifunctional molecular probes (MMPs), which integrate target recognition as well as diagnostic and therapeutic functions, introduce advanced molecular tools for TNBC theranostics. Using an MMP system, molecular drugs can be precisely delivered to the tumor site through a targeted ligand. Real-time dynamic monitoring of drug release achieved using imaging technology allows for the evaluation of drug enrichment at the tumor site. This approach enables accurate drug release, thereby improving the therapeutic effect. Therefore, this review summarizes the recent advancements in MMPs for TNBC theranostics, encompassing the design and synthesis of MMPs as well as their applications in the field of TNBC theranostics. Full article
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15 pages, 1621 KiB  
Review
Application of Scaffold-Based Drug Delivery in Oral Cancer Treatment: A Novel Approach
by Elham Saberian, Andrej Jenča, Adriána Petrášová, Hadi Zare-Zardini and Meysam Ebrahimifar
Pharmaceutics 2024, 16(6), 802; https://doi.org/10.3390/pharmaceutics16060802 - 14 Jun 2024
Viewed by 179
Abstract
This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, [...] Read more.
This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy. Full article
(This article belongs to the Special Issue Advanced Materials Science and Technology in Drug Delivery)
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21 pages, 4008 KiB  
Article
Liposome Encapsulation Enhances the Antidiabetic Efficacy of Silibinin
by Svetlana Dinić, Jelena Arambašić Jovanović, Aleksandra Uskoković, Aleksandra Jovanović, Nevena Grdović, Jovana Rajić, Marija Đorđević, Ana Sarić, Branko Bugarski, Melita Vidaković and Mirjana Mihailović
Pharmaceutics 2024, 16(6), 801; https://doi.org/10.3390/pharmaceutics16060801 - 13 Jun 2024
Viewed by 167
Abstract
Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the therapeutic application of silibinin is quite limited due to its poor bioavailability. In the present study, an attempt was made to improve the antidiabetic efficacy [...] Read more.
Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the therapeutic application of silibinin is quite limited due to its poor bioavailability. In the present study, an attempt was made to improve the antidiabetic efficacy of silibinin by its encapsulation in liposomal vesicles. The liposomes with a high encapsulation efficiency of silibinin (96%) and a zeta potential of −26.2 ± 0.6 mV were developed and studied using nicotinamide/streptozotocin-induced diabetic rats. Administration of silibinin-loaded liposomes to diabetic rats lowered glucose levels, increased insulin levels, and improved pancreatic islet architecture. The anti-inflammatory effect of silibinin-loaded liposomes was demonstrated by a decrease in serum C-reactive protein (CRP) levels and a reduced deposition of collagen fibers in the islets of diabetic rats. Furthermore, silibinin-loaded liposomes were more efficient in lowering glucose, alanine transaminase, triglyceride, and creatinine levels in diabetic rats than pure silibinin. In addition, silibinin-loaded liposomes had a significantly better effect on beta-cell mass and Glut2 glucose receptor distribution in diabetic islets than pure silibinin. The present results clearly show that liposome encapsulation of silibinin enhances its antidiabetic efficacy, which may contribute to the therapeutic benefit of silibinin in the treatment of diabetes and its complications. Full article
(This article belongs to the Special Issue Natural Pharmaceuticals Focused on Anti-inflammatory Activities)
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21 pages, 4436 KiB  
Article
Benznidazole-Loaded Polymeric Nanoparticles for Oral Chemotherapeutic Treatment of Chagas Disease
by Lucas Resende Dutra Sousa, Thays Helena Chaves Duarte, Viviane Flores Xavier, Aline Coelho das Mercês, Gabriel Maia Vieira, Maximiliano Delany Martins, Cláudia Martins Carneiro, Viviane Martins Rebello dos Santos, Orlando David Henrique dos Santos and Paula Melo de Abreu Vieira
Pharmaceutics 2024, 16(6), 800; https://doi.org/10.3390/pharmaceutics16060800 - 13 Jun 2024
Viewed by 304
Abstract
Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate [...] Read more.
Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 μg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product. Full article
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30 pages, 5739 KiB  
Article
In Vitro Metabolism and Transport Characteristics of Zastaprazan
by Min Seo Lee, Jihoon Lee, Minyoung Pang, John Kim, Hyunju Cha, Banyoon Cheon, Min-Koo Choi, Im-Sook Song and Hye Suk Lee
Pharmaceutics 2024, 16(6), 799; https://doi.org/10.3390/pharmaceutics16060799 - 13 Jun 2024
Viewed by 206
Abstract
Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this [...] Read more.
Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this compound in hepatocyte suspension and when 18 phase I metabolites and 5 phase II metabolites [i.e., N-dearylation (M6), hydroxylation (M1, M19, M21), dihydroxylation (M7, M8, M14, M22), trihydroxylation (M13, M18), hydroxylation and reduction (M20), dihydroxylation and reduction (M9, M16), hydrolysis (M23), hydroxylation and glucuronidation (M11, M15), hydroxylation and sulfation (M17), dihydroxylation and sulfation (M10, M12), N-dearylation and hydroxylation (M3, M4), N-dearylation and dihydroxylation (M5), and N-dearylation and trihydroxylation (M2)] were identified from JP-1366 incubation with the hepatocytes from humans, mice, rats, dogs, and monkeys. Based on the cytochrome P450 (CYP) screening test and immune-inhibition analysis with CYP antibodies, CYP3A4 and CYP3A5 played major roles in the metabolism of JP-1366 to M1, M3, M4, M6, M8, M9, M13, M14, M16, M18, M19, M21, and M22. CYP1A2, 2C8, 2C9, 2C19, and 2D6 played minor roles in the metabolism of JP-1366. UDP-glucuronosyltransferase (UGT) 2B7 and UGT2B17 were responsible for the glucuronidation of M1 to M15. However, JP-1366 and active metabolite M1 were not substrates for drug transporters such as organic cation transporter (OCT) 1/2, organic anion transporter (OAT) 1/3, organic anion transporting polypeptide (OATP)1B1/1B3, multidrug and toxic compound extrusion (MATE)1/2K, P-glycoprotein (P-gp), and breast cancer-resistant protein (BCRP). Only M1 showed substrate specificity for P-gp. The findings indicated that drug-metabolizing enzymes, particularly CYP3A4/3A5, may have a significant role in determining the pharmacokinetics of zastaprazan while drug transporters may only have a small impact on the absorption, distribution, and excretion of this compound. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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19 pages, 6384 KiB  
Article
Influence of Mechanical Loading on the Process of Tribochemical Action on Physicochemical and Biopharmaceutical Properties of Substances, Using Lacosamide as an Example: From Micronisation to Mechanical Activation
by Elena V. Uspenskaya, Ekaterina Kuzmina, Hoang Thi Ngoc Quynh, Maria A. Komkova, Ilaha V. Kazimova and Aleksey A. Timofeev
Pharmaceutics 2024, 16(6), 798; https://doi.org/10.3390/pharmaceutics16060798 - 13 Jun 2024
Viewed by 202
Abstract
Many physical and chemical properties of solids, such as strength, plasticity, dispersibility, solubility and dissolution are determined by defects in the crystal structure. The aim of this work is to study in situ dynamic, dispersion, chemical, biological and surface properties of lacosamide powder [...] Read more.
Many physical and chemical properties of solids, such as strength, plasticity, dispersibility, solubility and dissolution are determined by defects in the crystal structure. The aim of this work is to study in situ dynamic, dispersion, chemical, biological and surface properties of lacosamide powder after a complete cycle of mechanical loading by laser scattering, electron microscopy, FR-IR and biopharmaceutical approaches. The SLS method demonstrated the spontaneous tendency toward surface-energy reduction due to aggregation during micronisation. DLS analysis showed conformational changes of colloidal particles as supramolecular complexes depending on the loading time on the solid. SEM analysis demonstrated the conglomeration of needle-like lacosamide particles after 60 min of milling time and the transition to a glassy state with isotropy of properties by the end of the tribochemistry cycle. The following dynamic properties of lacosamide were established: elastic and plastic deformation boundaries, region of inhomogeneous deformation and fracture point. The ratio of dissolution-rate constants in water of samples before and after a full cycle of loading was 2.4. The lacosamide sample, which underwent a full cycle of mechanical loading, showed improved kinetics of API release via analysis of dissolution profiles in 0.1 M HCl medium. The observed activation-energy values of the cell-death biosensor process in aqueous solutions of the lacosamide samples before and after the complete tribochemical cycle were 207 kJmol−1 and 145 kJmol−1, respectively. The equilibrium time of dissolution and activation of cell-biosensor death corresponding to 20 min of mechanical loading on a solid was determined. The current study may have important practical significance for the transformation and management of the properties of drug substances in solid form and in solutions and for increasing the strength of drug matrices by pre-strain hardening via structural rearrangements during mechanical loading. Full article
(This article belongs to the Special Issue Novel Dry Powder Formulation and Delivery Systems)
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19 pages, 4927 KiB  
Article
Synthesis of Gd-DTPA Carborane-Containing Compound and Its Immobilization on Iron Oxide Nanoparticles for Potential Application in Neutron Capture Therapy
by Ilya V. Korolkov, Alexander Zaboronok, Kairat A. Izbasar, Zhangali A. Bekbol, Lana I. Lissovskaya, Alexandr V. Zibert, Rafael I. Shakirzyanov, Luiza N. Korganbayeva, Haolan Yang, Eiichi Ishikawa and Maxim V. Zdorovets
Pharmaceutics 2024, 16(6), 797; https://doi.org/10.3390/pharmaceutics16060797 - 12 Jun 2024
Viewed by 235
Abstract
Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has [...] Read more.
Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles, 2nd Edition)
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22 pages, 11192 KiB  
Article
Identification and Characterization of Critical Processing Parameters in the Fabrication of Double-Emulsion Poly(lactic-co-glycolic) Acid Microparticles
by Elizabeth R. Bentley, Stacia Subick, Michael Pezzillo, Stephen C. Balmert, Aidan Herbert and Steven R. Little
Pharmaceutics 2024, 16(6), 796; https://doi.org/10.3390/pharmaceutics16060796 - 12 Jun 2024
Viewed by 608
Abstract
In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved [...] Read more.
In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved products. One potential barrier to the clinical translation of these technologies is a lack of understanding with regard to the manufacturing process, hindering batch scale-up. To address this knowledge gap, we sought to first identify critical processing parameters in the manufacturing process of blank (no therapeutic drug) and protein-loaded double-emulsion poly(lactic-co-glycolic) acid MPs through a quality by design approach. We then utilized the design of experiments as a tool to systematically investigate the impact of these parameters on critical quality attributes (e.g., size, surface morphology, release kinetics, inner occlusion size, etc.) of blank and protein-loaded MPs. Our results elucidate that some of the most significant CPPs impacting many CQAs of double-emulsion MPs are those within the primary or single-emulsion process (e.g., inner aqueous phase volume, solvent volume, etc.) and their interactions. Furthermore, our results indicate that microparticle internal structure (e.g., inner occlusion size, interconnectivity, etc.) can heavily influence protein release kinetics from double-emulsion MPs, suggesting it is a crucial CQA to understand. Altogether, this study identifies several important considerations in the manufacturing and characterization of double-emulsion MPs, potentially enhancing their translation. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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12 pages, 3160 KiB  
Review
Nano-Delivery of Immunogenic Cell Death Inducers and Immune Checkpoint Blockade Agents: Single-Nanostructure Strategies for Enhancing Immunotherapy
by Yujeong Moon, Hanhee Cho and Kwangmeyung Kim
Pharmaceutics 2024, 16(6), 795; https://doi.org/10.3390/pharmaceutics16060795 - 12 Jun 2024
Viewed by 210
Abstract
Cancer immunotherapy has revolutionized oncology by harnessing the patient’s immune system to target and eliminate cancer cells. However, immune checkpoint blockades (ICBs) face limitations such as low response rates, particularly in immunologically ‘cold’ tumors. Enhancing tumor immunogenicity through immunogenic cell death (ICD) inducers [...] Read more.
Cancer immunotherapy has revolutionized oncology by harnessing the patient’s immune system to target and eliminate cancer cells. However, immune checkpoint blockades (ICBs) face limitations such as low response rates, particularly in immunologically ‘cold’ tumors. Enhancing tumor immunogenicity through immunogenic cell death (ICD) inducers and advanced drug delivery systems represents a promising solution. This review discusses the development and application of various nanocarriers, including polymeric nanoparticles, liposomes, peptide-based nanoparticles, and inorganic nanoparticles, designed to deliver ICD inducers and ICBs effectively. These nanocarriers improve therapeutic outcomes by converting cold tumors into hot tumors, thus enhancing immune responses and reducing systemic toxicity. By focusing on single-nanoparticle systems that co-deliver both ICD inducers and ICBs, this review highlights their potential in achieving higher drug concentrations at tumor sites, improving pharmacokinetics and pharmacodynamics, and facilitating clinical translation. Future research should aim to optimize these nanocarrier systems for better in vivo performance and clinical applications, ultimately advancing cancer immunotherapy. Full article
(This article belongs to the Special Issue Nanomedicines in Cancer Therapy)
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2 pages, 268 KiB  
Editorial
New Challenges in Ocular Drug Delivery
by Rosario Pignatello, Hugo Almeida, Debora Santonocito and Carmelo Puglia
Pharmaceutics 2024, 16(6), 794; https://doi.org/10.3390/pharmaceutics16060794 - 11 Jun 2024
Viewed by 194
Abstract
The clinical treatment of diseases affecting the eye globe, and specifically the retina and posterior eye segment, is often hindered by the physiological protection structures and mechanisms of the organ, as well as by the unsuitable physico-chemical features of the active molecules [...] [...] Read more.
The clinical treatment of diseases affecting the eye globe, and specifically the retina and posterior eye segment, is often hindered by the physiological protection structures and mechanisms of the organ, as well as by the unsuitable physico-chemical features of the active molecules [...] Full article
(This article belongs to the Topic New Challenges in Ocular Drug Delivery)
29 pages, 2532 KiB  
Review
MOF-Based Platform for Kidney Diseases: Advances, Challenges, and Prospects
by Li-Er Deng, Manli Guo, Yijun Deng, Ying Pan, Xiaoxiong Wang, Govindhan Maduraiveeran, Jianqiang Liu and Chengyu Lu
Pharmaceutics 2024, 16(6), 793; https://doi.org/10.3390/pharmaceutics16060793 - 11 Jun 2024
Viewed by 231
Abstract
Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance [...] Read more.
Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
6 pages, 183 KiB  
Editorial
Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy
by Gellert Balazs Karvaly and Barna Vásárhelyi
Pharmaceutics 2024, 16(6), 792; https://doi.org/10.3390/pharmaceutics16060792 - 11 Jun 2024
Viewed by 226
Abstract
The philosophy, practice, and clinical impact of therapeutic drug monitoring (TDM) has changed profoundly with the appearance of widely available and, in a technical sense, commonly applicable modeling, simulation, and dosing software tools in the past decade [...] Full article
14 pages, 2993 KiB  
Article
Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment
by Nicolette Frank, Douglas Dickinson, Garrison Lovett, Yutao Liu, Hongfang Yu, Jingwen Cai, Bo Yao, Xiaocui Jiang and Stephen Hsu
Pharmaceutics 2024, 16(6), 791; https://doi.org/10.3390/pharmaceutics16060791 - 11 Jun 2024
Viewed by 288
Abstract
Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19 (PASC), also referred to as long COVID. According to the US National Research Action Plan on Long COVID 2022, [...] Read more.
Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19 (PASC), also referred to as long COVID. According to the US National Research Action Plan on Long COVID 2022, up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to these symptoms, leading to a USD 50 billion annual loss of salary. Neurological symptoms associated with long COVID result from persistent infection with SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous system (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in olfactory mucosa. Recently published clinical data demonstrate that only 5% of long COVID anosmia patients have fully recovered during the past 2 years, and 10.4% of COVID patients are still symptomatic 18 months post-infection. Our group demonstrated that epigallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activity against human coronavirus, suggesting that this green-tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to restoration of neurologic functions. The objective of the current study was to evaluate the mucociliary safety of the EC16m nasal nanoformulations and their efficacy against human coronavirus. Methods: Nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using the MucilAir human nasal model; contact antiviral activity and post-infection inhibition against the OC43 viral strain were assessed by the TCID50 assay for cytopathic effect on MRC-5 cells. Results: The saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference compared to saline (0.9% NaCl) with respect to tissue integrity, cytotoxicity, and cilia beat frequency. A 5 min contact resulted in 99.9% inactivation of β-coronavirus OC43. OC43 viral replication was inhibited by >90% after infected MRC-5 cells were treated with the formulations. Conclusion: The saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety properties comparable to saline, a solution widely used for nasal applications. Full article
(This article belongs to the Special Issue Nanoparticle-Mediated Targeted Drug Delivery Systems)
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28 pages, 1069 KiB  
Review
Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology
by Imola-Rebeka Turac, Alina Porfire, Sonia Iurian, Andrea Gabriela Crișan, Tibor Casian, Rareș Iovanov and Ioan Tomuță
Pharmaceutics 2024, 16(6), 790; https://doi.org/10.3390/pharmaceutics16060790 - 11 Jun 2024
Viewed by 494
Abstract
Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active [...] Read more.
Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones. This review assesses the newest production technologies and briefly describes the in vitro and in vivo evaluation methods, with the aim of providing a better overall understanding of GRDDSs as a novel emerging strategy for targeted drug delivery. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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17 pages, 2768 KiB  
Article
Targeting S. aureus Extracellular Vesicles: A New Putative Strategy to Counteract Their Pathogenic Potential
by Giulio Petronio Petronio, Maria Di Naro, Noemi Venditti, Antonio Guarnieri, Marco Alfio Cutuli, Irene Magnifico, Alessandro Medoro, Emanuele Foderà, Daniela Passarella, Daria Nicolosi and Roberto Di Marco
Pharmaceutics 2024, 16(6), 789; https://doi.org/10.3390/pharmaceutics16060789 - 11 Jun 2024
Viewed by 395
Abstract
Long-term inflammatory skin disease atopic dermatitis is characterized by dry skin, itching, and eczematous lesions. During inflammation skin barrier protein impairment promotes S. aureus colonisation in the inflamed skin, worsening AD patient’s clinical condition. Proteomic analysis revealed the presence of several immune evasion [...] Read more.
Long-term inflammatory skin disease atopic dermatitis is characterized by dry skin, itching, and eczematous lesions. During inflammation skin barrier protein impairment promotes S. aureus colonisation in the inflamed skin, worsening AD patient’s clinical condition. Proteomic analysis revealed the presence of several immune evasion proteins and virulence factors in S. aureus extracellular vesicles (EVs), suggesting a possible role for these proteins in the pathophysiology of atopic dermatitis. The objective of this study is to assess the efficacy of a wall fragment obtained from a patented strain of C. acnes DSM28251 (c40) and its combination with a mucopolysaccharide carrier (HAc40) in counteract the pathogenic potential of EVs produced by S. aureus ATCC 14458. Results obtained from in vitro studies on HaCaT keratinocyte cells showed that HAc40 and c40 treatment significantly altered the size and pathogenicity of S. aureus EVs. Specifically, EVs grew larger, potentially reducing their ability to interact with the target cells and decreasing cytotoxicity. Additionally, the overexpression of the tight junctions mRNA zona occludens 1 (ZO1) and claudin 1 (CLDN1) following EVs exposure was decreased by HAc40 and c40 treatment, indicating a protective effect on the epidermal barrier’s function. These findings demonstrate how Hac40 and c40 may mitigate the harmful effects of S. aureus EVs. Further investigation is needed to elucidate the exact mechanisms underlying this interaction and explore the potential clinical utility of c40 and its mucopolysaccharide carrier conjugate HAc40 in managing atopic dermatitis. Full article
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18 pages, 2981 KiB  
Article
Formulation and Evaluation of Polysaccharide Microparticles for the Controlled Release of Propranolol Hydrochloride
by Aneta Stojmenovski, Biljana Gatarić, Sonja Vučen, Maja Railić, Veljko Krstonošić, Radovan Kukobat, Maja Mirjanić, Ranko Škrbić and Anđelka Račić
Pharmaceutics 2024, 16(6), 788; https://doi.org/10.3390/pharmaceutics16060788 - 11 Jun 2024
Viewed by 281
Abstract
Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need [...] Read more.
Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug’s short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary. Full article
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15 pages, 912 KiB  
Review
Exploring the Potential Use of Natural Products Together with Alkalization in Cancer Therapy
by Masahide Isowa, Reo Hamaguchi, Ryoko Narui, Hiromasa Morikawa, Toshihiro Okamoto and Hiromi Wada
Pharmaceutics 2024, 16(6), 787; https://doi.org/10.3390/pharmaceutics16060787 - 10 Jun 2024
Viewed by 323
Abstract
Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. [...] Read more.
Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with supplementation with natural products may confer benefits to cancer patients, by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings. Full article
(This article belongs to the Special Issue Natural Products for Anticancer Application)
17 pages, 1894 KiB  
Article
Improving the Antimicrobial Potency of Berberine for Endodontic Canal Irrigation Using Polymeric Nanoparticles
by Célia Marques, Liliana Grenho, Maria Helena Fernandes and Sofia A. Costa Lima
Pharmaceutics 2024, 16(6), 786; https://doi.org/10.3390/pharmaceutics16060786 - 9 Jun 2024
Viewed by 432
Abstract
To address the challenges posed by biofilm presence and achieve a substantial reduction in bacterial load within root canals during endodontic treatment, various irrigants, including nanoparticle suspensions, have been recommended. Berberine (BBR), a natural alkaloid derived from various plants, has demonstrated potential applications [...] Read more.
To address the challenges posed by biofilm presence and achieve a substantial reduction in bacterial load within root canals during endodontic treatment, various irrigants, including nanoparticle suspensions, have been recommended. Berberine (BBR), a natural alkaloid derived from various plants, has demonstrated potential applications in dentistry treatments due to its prominent antimicrobial, anti-inflammatory, and antioxidant properties. This study aimed to produce and characterize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with berberine and evaluate its antimicrobial activity against relevant endodontic pathogens, Enterococcus faecalis, and Candida albicans. Additionally, its cytocompatibility using gingival fibroblasts was assessed. The polymeric nanoparticle was prepared by the nanoprecipitation method. Physicochemical characterization revealed spheric nanoparticles around 140 nm with ca, −6 mV of surface charge, which was unaffected by the presence of BBR. The alkaloid was successfully incorporated at an encapsulation efficiency of 77% and the designed nanoparticles were stable upon 20 weeks of storage at 4 °C and 25 °C. Free BBR reduced planktonic growth at ≥125 μg/mL. Upon incorporation into PLGA nanoparticles, 20 μg/mL of [BBR]-loaded nanoparticles lead to a significant reduction, after 1 h of contact, of both planktonic bacteria and yeast. Sessile cells within biofilms were also considered. At 30 and 40 μg/mL, [BBR]-loaded PLGA nanoparticles reduced the viability of the sessile endodontic bacteria, upon 24 h of exposure. The cytotoxicity of BBR-loaded nanoparticles to oral fibroblasts was negligible. The novel berberine-loaded polymeric nanoparticles hold potential as a promising supplementary approach in the treatment of endodontic infections. Full article
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15 pages, 4102 KiB  
Article
Cytotoxic Effects of Doxorubicin on Cancer Cells and Macrophages Depend Differently on the Microcarrier Structure
by Daria Kalenichenko, Irina Kriukova, Alexander Karaulov, Igor Nabiev and Alyona Sukhanova
Pharmaceutics 2024, 16(6), 785; https://doi.org/10.3390/pharmaceutics16060785 - 9 Jun 2024
Viewed by 416
Abstract
Microparticles are versatile carriers for controlled drug delivery in personalized, targeted therapy of various diseases, including cancer. The tumor microenvironment contains different infiltrating cells, including immune cells, which can affect the efficacy of antitumor drugs. Here, prototype microparticle-based systems for the delivery of [...] Read more.
Microparticles are versatile carriers for controlled drug delivery in personalized, targeted therapy of various diseases, including cancer. The tumor microenvironment contains different infiltrating cells, including immune cells, which can affect the efficacy of antitumor drugs. Here, prototype microparticle-based systems for the delivery of the antitumor drug doxorubicin (DOX) were developed, and their cytotoxic effects on human epidermoid carcinoma cells and macrophages derived from human leukemia monocytic cells were compared in vitro. DOX-containing calcium carbonate microparticles with or without a protective polyelectrolyte shell and polyelectrolyte microcapsules of about 2.4–2.5 μm in size were obtained through coprecipitation and spontaneous loading. All the microstructures exhibited a prolonged release of DOX. An estimation of the cytotoxicity of the DOX-containing microstructures showed that the encapsulation of DOX decreased its toxicity to macrophages and delayed the cytotoxic effect against tumor cells. The DOX-containing calcium carbonate microparticles with a protective polyelectrolyte shell were more toxic to the cancer cells than DOX-containing polyelectrolyte microcapsules, whereas, for the macrophages, the microcapsules were most toxic. It is concluded that DOX-containing core/shell microparticles with an eight-layer polyelectrolyte shell are optimal drug microcarriers due to their low toxicity to immune cells, even upon prolonged incubation, and strong delayed cytotoxicity against tumor cells. Full article
(This article belongs to the Topic Recent Advances in Anticancer Strategies)
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21 pages, 6251 KiB  
Article
Preparation and Evaluation of Inhalable Microparticles with Improved Aerodynamic Performance and Dispersibility Using L-Leucine and Hot-Melt Extrusion
by Jin-Hyuk Jeong, Ji-Su Kim, Yu-Rim Choi, Dae Hwan Shin, Ji-Hyun Kang, Dong-Wook Kim, Yun-Sang Park and Chun-Woong Park
Pharmaceutics 2024, 16(6), 784; https://doi.org/10.3390/pharmaceutics16060784 - 8 Jun 2024
Viewed by 394
Abstract
Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility [...] Read more.
Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery. Full article
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17 pages, 2526 KiB  
Article
Geometry-Driven Fabrication of Mini-Tablets via 3D Printing: Correlating Release Kinetics with Polyhedral Shapes
by Young-Jin Kim, Yu-Rim Choi, Ji-Hyun Kang, Yun-Sang Park, Dong-Wook Kim and Chun-Woong Park
Pharmaceutics 2024, 16(6), 783; https://doi.org/10.3390/pharmaceutics16060783 - 8 Jun 2024
Viewed by 342
Abstract
The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT [...] Read more.
The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R2 = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)
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