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Pharmaceutics
Volume 17
Issue 8
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Pharmaceutics, Volume 17, Issue 8 (August 2025) – 142 articles

Cover Story (view full-size image): Theranostic nanomedicines manufacturing on a scale needed for clinical translation is challenging. The presented nanoemulsions, formulated with non-immunogenic, safe, coconut oil, an FDA-approved COX-2 inhibitor, celecoxib, as the therapeutic agent, and a clinical-grade indocyanine green near-infrared fluorescent dye, as the diagnostic component, serve as a model theranostic nanomedicine. The Quality by Design methods applied here address these challenges. Failure, Modes, Effects, and Criticality Analysis (FMECA) and multiple linear regression (MLR) predictive modeling methods led to a scalable, stable, and safe nanoemulsion with high drug loading applicable for parenteral use in inflammatory diseases. The presented QbD methods serve as a roadmap for future nanomedicine manufacturing and development. View this paper
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45 pages, 1496 KiB  
Review
Integrating Graphene Oxide and Mesenchymal Stem Cells in 3D-Printed Systems for Drug Delivery and Tissue Regeneration
by Igor Soares Gianini Grecca, Vitor Fernando Bordin Miola, Júlia Carolina Ferreira, Thiago Rissato Vinholo, Laira Mireli Dias da Silva, Paulo Gabriel Friedrich Totti, Silvia Helena Soares Gianini, Maricelma da Silva Soares de Souza, Juliana da Silva Soares de Souza, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Caio Sérgio Galina Spilla, Marcelo Dib Bechara, Domingos Donizeti Roque, Eliana de Souza Bastos Mazuqueli Pereira and Karina Torres Pomini
Pharmaceutics 2025, 17(8), 1088; https://doi.org/10.3390/pharmaceutics17081088 - 21 Aug 2025
Viewed by 131
Abstract
Mesenchymal stem cells (MSCs) represent a promising strategy in the field of regenerative medicine due to their multipotent differentiation capacity and immunomodulatory properties. The interaction of these cells with the extracellular matrix (ECM) and biomaterials, notably graphene oxide (GO), has proven decisive in [...] Read more.
Mesenchymal stem cells (MSCs) represent a promising strategy in the field of regenerative medicine due to their multipotent differentiation capacity and immunomodulatory properties. The interaction of these cells with the extracellular matrix (ECM) and biomaterials, notably graphene oxide (GO), has proven decisive in modulating cell behavior, with the potential to optimize tissue regeneration processes. This review was conducted using the MEDLINE, Scopus, and Cochrane databases, covering studies published between 2018 and 2025, from which seven studies met the inclusion criteria, with an emphasis on in vitro and in vivo investigations regarding the association between GO and MSCs. The main findings demonstrate that GO, particularly when conjugated with polymers such as poly(L-lactic acid) (PLLA), enhances cell adhesion, stimulates proliferation, and promotes the osteogenic differentiation of MSCs, in addition to positively modulating intracellular signaling pathways. However, significant gaps remain in understanding the mechanisms and safety of GO’s therapeutic use in association with MSCs. Therefore, this review reinforces the need for further studies to deepen the characterization of the bioactive properties of GO-MSCs, aiming to enable safer and more effective clinical applications. Full article
(This article belongs to the Special Issue Cutting-Edge 3D Printing Technology for Drug Delivery and Tissue Engineering)
35 pages, 2860 KiB  
Review
An Update on Novel Drug Delivery Systems for the Management of Glaucoma
by Harshilkumar S. Jani, Ketan Ranch, Radhika Pandya, Yashkumar Patel, Sai H. S. Boddu, Amit K. Tiwari, Shery Jacob and Haya Khader Ahmad Yasin
Pharmaceutics 2025, 17(8), 1087; https://doi.org/10.3390/pharmaceutics17081087 - 21 Aug 2025
Viewed by 190
Abstract
Glaucoma is recognized as a chronic optic neuropathy marked by progressive optic nerve degeneration, loss of retinal ganglion cells (RGCs, the neurons responsible for transmitting visual information from the eye to the brain), disruptions in optic disc blood supply, and changes in glial [...] Read more.
Glaucoma is recognized as a chronic optic neuropathy marked by progressive optic nerve degeneration, loss of retinal ganglion cells (RGCs, the neurons responsible for transmitting visual information from the eye to the brain), disruptions in optic disc blood supply, and changes in glial cell activation. It ranks as the second most prevalent cause of irreversible visual impairment worldwide and is a resultant of increased intraocular pressure (IOP). Addressing this condition proves complex due to the inherent hindrances posed by ocular barriers, which curtail the entry of drugs into the eye. Diverse carriers such as inorganic nanoparticles, polymeric nanocarriers, hydrogels, and contact lens-based systems with distinct physical and chemical attributes are being studied for drug delivery. They have shown enhanced ocular drug bioavailability through higher penetration across ocular tissues, prolonged retention in the precorneal space, sustained drug release, and targeted delivery to specific tissues. These ingenious delivery systems can be deployed through various administration routes—intravitreal or periocular injections or systemic administration—enabling the drugs to reach affected areas, aiding in the regeneration of compromised optical nerves. This review presents a comprehensive exploration of contemporary strides in ocular delivery formulations pertaining to glaucoma. This encompasses an examination of various nanocarrier typologies, delivery routes, in vitro and in vivo effectiveness, clinical applicability, and a forward-looking perspective into potential future developments. Full article
(This article belongs to the Special Issue Novel Approaches to Drug Delivery in Ophthalmic Disorders)
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39 pages, 2665 KiB  
Review
The Potential of Amphiphilic Cyclodextrins as Carriers for Therapeutic Purposes: A Short Overview
by Ramona Daniela Pârvănescu, Marius Păpurică, Ionica Oana Alexa, Cristina Adriana Dehelean, Codruța Șoica, Elena Alina Moacă, Adriana Ledeți, Mirela Voicu, Dorina Coricovac and Cristina Trandafirescu
Pharmaceutics 2025, 17(8), 1086; https://doi.org/10.3390/pharmaceutics17081086 - 21 Aug 2025
Viewed by 161
Abstract
Cyclodextrins, since their discovery in the late 19th century, have gained tremendous interest in biomedical research, beginning with their recognition as safe pharmaceutical excipients, and continuing with exploiting their potential for enhancing the therapeutic response of active pharmaceutical ingredients, and also to be [...] Read more.
Cyclodextrins, since their discovery in the late 19th century, have gained tremendous interest in biomedical research, beginning with their recognition as safe pharmaceutical excipients, and continuing with exploiting their potential for enhancing the therapeutic response of active pharmaceutical ingredients, and also to be used as drugs for specific medical purposes. This review presents an integrative perspective on amphiphilic cyclodextrins, the manuscript being divided into two parts, one devoted to the properties of amphiphilic cyclodextrins, while the second one is dedicated to their biomedical applications, with an emphasis on cancer therapy. Full article
(This article belongs to the Special Issue Recent Insights Concerning the Use of Supramolecular Systems for Biomedical Applications)
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16 pages, 1525 KiB  
Article
Physiologically Based Pharmacokinetic Modeling to Assess Perpetrator and Victim Cytochrome P450 2C Induction Risk
by Marina Slavsky, Aniruddha Sunil Karve and Niresh Hariparsad
Pharmaceutics 2025, 17(8), 1085; https://doi.org/10.3390/pharmaceutics17081085 - 21 Aug 2025
Viewed by 164
Abstract
Background: Accurate assessment of CYP2C induction-mediated drug–drug interactions (DDIs) remains a challenge, despite the importance of CYP2C enzymes in drug metabolism. Limitations in available models and scarce clinical induction data have hampered quantitative preclinical DDI risk evaluation. Methods: In this study, the authors [...] Read more.
Background: Accurate assessment of CYP2C induction-mediated drug–drug interactions (DDIs) remains a challenge, despite the importance of CYP2C enzymes in drug metabolism. Limitations in available models and scarce clinical induction data have hampered quantitative preclinical DDI risk evaluation. Methods: In this study, the authors utilized an all-human hepatocyte triculture system to capture CYP2C induction using the perpetrators rifampicin, efavirenz, carbamazepine, and apalutamide. In vitro induction parameters were quantified by measuring changes in both mRNA and enzyme activities for CYP2C8, CYP2C9, and CYP2C19. These induction parameters, along with CYP-specific intrinsic clearance (CLint) for the victim compounds, were incorporated into a physiologically based pharmacokinetic (PBPK) model, and pharmacokinetics (PK) of known CYP2C substrates were predicted with and without co-administration of perpetrator compounds using clinical dosing regimens. The results were quantitatively compared with the currently utilized mechanistic static modeling (MSM) approach and the reported clinical DDI outcomes. Results: By incorporating the measured fm of CYP2C substrates into PBPK modeling, we observed a lower propensity to over- or underpredict the exposure of these substrates as victims of CYP2C induction-based DDIs when co-administered with known perpetrators, which resulted in an excellent correlation to observed clinical outcomes. The MSM approach predicted the CYP3A4 induction-based DDI risk accurately but could not capture CYP2C induction with similar precision. Conclusions: Overall, this is the first study that demonstrates the utility of PBPK modeling as a complementary approach to MSM for CYP2C induction-based DDI risk assessment. Full article
(This article belongs to the Special Issue Development of Physiologically Based Pharmacokinetic (PBPK) Modeling)
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25 pages, 3433 KiB  
Article
Exploring miRNA Research in Colorectal Cancer: Insights from a Bibliometric Analysis
by Emanuele Piccinno, Michelangelo Aloisio, Viviana Scalavino, Francesco Russo, Gianluigi Giannelli, Davide Guido and Grazia Serino
Pharmaceutics 2025, 17(8), 1084; https://doi.org/10.3390/pharmaceutics17081084 - 21 Aug 2025
Viewed by 122
Abstract
Background/Objectives: Despite advances in diagnosis and treatment, colorectal cancer (CRC) remains one of the most prevalent and challenging malignancies worldwide. The dysregulation of microRNAs (miRNAs) has emerged as a critical factor in CRC onset, progression, and therapeutic resistance. This study aims to [...] Read more.
Background/Objectives: Despite advances in diagnosis and treatment, colorectal cancer (CRC) remains one of the most prevalent and challenging malignancies worldwide. The dysregulation of microRNAs (miRNAs) has emerged as a critical factor in CRC onset, progression, and therapeutic resistance. This study aims to provide an overview of global research trends on miRNAs in CRC, (i) identifying the most studied miRNAs, (ii) exploring under-investigated areas, and (iii) highlighting emerging themes and potential future directions. Methods: To assess the evolution of the global miRNA–CRC research trends, we conducted a bibliometric analysis of 828 CRC–miRNA-focused articles published between 2008 and 2024, sourced from the Scopus database. Bibliometric mapping was performed using the R/Bibliometrix package and by leveraging a customized Python-based pipeline, which is useful for extracting and validating miRNA identifiers (miRNA IDs) based on the miRBase database. This miRNA ID-related approach enabled us to systematically identify the most frequently studied miRNAs over time while highlighting underexplored miRNA. Results: The analysis revealed a substantial and accelerating publication growth rate, delineating three major phases in CRC–miRNA research. China emerged as the leading contributor in terms of the publication volume. miR-21, miR-34a, and miR-195-5p were among the most frequently studied miRNAs, underscoring their relevance to CRC biology and therapy. Keyword and citation analyses identified key thematic areas, such as cell proliferation, epithelial–mesenchymal transition, and chemoresistance, especially to oxaliplatin and 5-fluorouracil. Emerging research frontiers included ferroptosis, ceRNA networks, and exosome-mediated miRNA transport. An analysis of the collaborations indicated strong intra-national collaborations, with room for expanding international research networks. Conclusions: This study provides an in-depth bibliometric landscape of the CRC-related miRNA research by highlighting influential studies and journals while identifying gaps and underexplored topics. These insights offer valuable guidance for future translational and clinical research on this topic. Full article
(This article belongs to the Special Issue Recent Advances in Gastrointestinal Disease: Insights into Drug Delivery and Cellular and Molecular Mechanisms for Therapy)
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4 pages, 152 KiB  
Editorial
From Data to Dose: Diversity in Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy
by Gellert Balazs Karvaly and Barna Vásárhelyi
Pharmaceutics 2025, 17(8), 1083; https://doi.org/10.3390/pharmaceutics17081083 - 21 Aug 2025
Viewed by 90
Abstract
In the past few years, interest in therapeutic drug monitoring (TDM) and the pharmacokinetics-based individualization of drug therapy has gained increased impetus [...] Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy, 2nd Edition)
15 pages, 1023 KiB  
Review
Stimuli-Responsive, Cell-Mediated Drug Delivery Systems: Engineering Smart Cellular Vehicles for Precision Therapeutics
by Samson Sitheni Mashele
Pharmaceutics 2025, 17(8), 1082; https://doi.org/10.3390/pharmaceutics17081082 - 21 Aug 2025
Viewed by 121
Abstract
Stimuli-responsive, cell-mediated drug delivery systems represent a dynamic interface between biological functionality and engineered control. Leveraging the inherent targeting properties of erythrocytes, immune cells, stem cells, and exosomes, these systems offer a promising strategy for precise therapeutic delivery. In this review, we provide [...] Read more.
Stimuli-responsive, cell-mediated drug delivery systems represent a dynamic interface between biological functionality and engineered control. Leveraging the inherent targeting properties of erythrocytes, immune cells, stem cells, and exosomes, these systems offer a promising strategy for precise therapeutic delivery. In this review, we provide a comprehensive analysis of the design principles and biological underpinnings of stimuli-responsive carriers that release payloads in response to endogenous triggers (e.g., pH, redox, enzymatic activity) or external stimuli (e.g., light, ultrasound, magnetic fields). We further examine current strategies for loading and functionalizing cellular carriers, highlight key therapeutic applications across oncology and regenerative medicine, and assess translational progress and regulatory challenges. This review underscores the emerging clinical potential of intelligent cell-based delivery vehicles and outlines future directions for their optimization and implementation. Full article
(This article belongs to the Special Issue Cell-Mediated Delivery Systems)
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17 pages, 1402 KiB  
Article
Once-Daily Versus Four-Times-Daily Intravenous Busulfan with Therapeutic Drug Monitoring as Conditioning for Hematopoietic Cell Transplantation in Children
by Safaa Bazbaz, Irina Zaidman, Ehud Even-Or, Polina Stepensky, Razan Sakran, Daniel Kurnik and Gefen Aldouby-Bier
Pharmaceutics 2025, 17(8), 1081; https://doi.org/10.3390/pharmaceutics17081081 - 21 Aug 2025
Viewed by 114
Abstract
Background/Objectives: Busulfan is a key component of myeloablative conditioning regimens in hematopoietic stem cell transplantation (HSCT) for pediatric patients with acute myeloid leukemia, solid tumors, and certain non-malignant diseases. This study compares the clinical outcomes of once-daily (BU1) versus four-times-daily (BU4) busulfan dosing [...] Read more.
Background/Objectives: Busulfan is a key component of myeloablative conditioning regimens in hematopoietic stem cell transplantation (HSCT) for pediatric patients with acute myeloid leukemia, solid tumors, and certain non-malignant diseases. This study compares the clinical outcomes of once-daily (BU1) versus four-times-daily (BU4) busulfan dosing regimens in pediatric HSCT recipients. Methods: A retrospective analysis was conducted on 70 pediatric patients who underwent HSCT at Hadassah Medical Center between June 2018 and October 2023. Thirty-five patients received the BU4 regimen, and 35 received BU1. The primary endpoint was 100-day event-free survival (EFS). Results: There was no statistically significant difference in 100-day event-free survival between the BU1 group (88.6%) and the BU4 group (85.7%; p = 0.768). Similarly, no significant differences were found in time to neutrophil engraftment (p = 0.251) or platelet engraftment (p = 0.688). Sinusoidal obstruction syndrome (SOS) occurred in 17.1% of patients in each group. No significant differences were observed in the increase in liver enzyme levels (p = 1.0). The incidence of acute graft-versus-host disease was comparable between the groups (41.9% for BU1 vs. 40.0% for BU4; p = 0.878). Conclusions: Once-daily and four-times-daily busulfan regimens demonstrated comparable clinical outcomes in terms of efficacy and adverse events. Further prospective studies are needed to validate these findings. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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26 pages, 1086 KiB  
Review
Nanotechnology-Enhanced Sunscreens: Balancing Efficacy, Safety, and Environmental Impact
by Ruchi Khobragade, Anis Ahmad Chaudhary, Mohamed A. M. Ali, Mayur Kale, Neha Raut, Pratik Ghive, Hassan A. Rudayni, Krutika Nagpurkar, Milind Umekar and Rashmi Trivedi
Pharmaceutics 2025, 17(8), 1080; https://doi.org/10.3390/pharmaceutics17081080 - 21 Aug 2025
Viewed by 140
Abstract
Sunscreen protects skin from harmful Ultra Violet (UV) rays, preventing skin diseases like cancer and premature aging. This review explores the role of nanotechnology in enhancing sunscreen formulations by incorporating green and sustainable ingredients. Nanoparticles such as titanium dioxide and zinc oxide effectively [...] Read more.
Sunscreen protects skin from harmful Ultra Violet (UV) rays, preventing skin diseases like cancer and premature aging. This review explores the role of nanotechnology in enhancing sunscreen formulations by incorporating green and sustainable ingredients. Nanoparticles such as titanium dioxide and zinc oxide effectively reflect UV rays, improving protection while minimizing white residue, thereby enhancing aesthetics, stability, and efficacy. Recent advancements in formulation include lipid-based and polymer-based nanosystems that improve the delivery of active ingredients, offering multifunctional benefits. Additionally, modern sunscreens integrate anti-aging and antioxidant properties, reflecting the trend toward hybrid formulations with multiple skin benefits. The review also examines recent patents, highlighting innovations in nanotechnology-driven sunscreen formulations and delivery systems. Safety and regulatory concerns are critically analyzed, focusing on public perception of nanoparticles and their environmental impact. Issues such as manufacturing challenges and consumer hesitancy toward nano-scaled formulations due to safety considerations are also discussed. While nanotechnology presents significant potential in advancing sun protection, the review underscores the importance of balancing innovation with safety and sustainability. Ultimately, it serves as a guide for future research directions in nano-based sunscreens, advocating for responsible and informed development in the field. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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52 pages, 1938 KiB  
Review
Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Anticancer Phytochemical Delivery: Advances, Challenges, and Future Prospects
by Shery Jacob, Rekha Rao, Bapi Gorain, Sai H. S. Boddu and Anroop B. Nair
Pharmaceutics 2025, 17(8), 1079; https://doi.org/10.3390/pharmaceutics17081079 - 21 Aug 2025
Viewed by 260
Abstract
Phytochemicals exhibit a broad spectrum of pharmacological activities, including significant anticancer potential. However, their clinical translation is often hampered by poor aqueous solubility, low bioavailability, and chemical instability. Lipid-based nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have proven to [...] Read more.
Phytochemicals exhibit a broad spectrum of pharmacological activities, including significant anticancer potential. However, their clinical translation is often hampered by poor aqueous solubility, low bioavailability, and chemical instability. Lipid-based nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have proven to be effective strategies for addressing these challenges. These nanocarriers improve the solubility, stability, and bioavailability of phytochemical-based anticancer agents, while enabling controlled and tumor-specific drug release. Encapsulation of anticancer phytochemicals such as curcumin, quercetin, resveratrol, silymarin, and naringenin in SLNs and NLCs has demonstrated improved therapeutic efficacy, cellular uptake, and reduced systemic toxicity. Co-delivery strategies, combining multiple phytochemicals or phytochemical–synthetic drug pairs, further contribute to synergistic anticancer effects, dose reduction, and minimized side effects, particularly important in complex cancers such as glioblastoma, breast, and colon cancers. This review presents a comparative overview of SLNs and NLCs in terms of formulation methods, in vitro characterization, and classification of key phytochemicals based on chemical structure and botanical sources. The roles of these lipidic carriers in enhancing anticancer activity, challenges in formulation, and recent patent filings are discussed to highlight ongoing innovations. Additionally, hybrid lipid–polymer nanoparticles are introduced as next-generation carriers combining the benefits of both systems. Future research should aim to develop scalable, biomimetic, and stimuli-responsive nanostructures through advanced surface engineering. Collaborative interdisciplinary efforts and regulatory harmonization are essential to translate these lipid-based carriers into clinically viable platforms for anticancer phytochemical delivery. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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17 pages, 2746 KiB  
Article
Development of PBPK Population Model for End-Stage Renal Disease Patients to Inform OATP1B-, BCRP-, P-gp-, and CYP3A4-Mediated Drug Disposition with Individual Influencing Factors
by Yujie Wu, Weijie Kong, Jiayu Li, Xiaoqiang Xiang, Hao Liang and Dongyang Liu
Pharmaceutics 2025, 17(8), 1078; https://doi.org/10.3390/pharmaceutics17081078 - 20 Aug 2025
Viewed by 263
Abstract
Background/Objective: Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool for predicting pharmacokinetics (PK) to support drug development and precision medicine. However, it has not been established for non-renal clearance pathways in patients with end-stage renal disease (ESRD), a population that bears heavy [...] Read more.
Background/Objective: Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool for predicting pharmacokinetics (PK) to support drug development and precision medicine. However, it has not been established for non-renal clearance pathways in patients with end-stage renal disease (ESRD), a population that bears heavy medication burden and is thereby at high risk for drug–drug–disease interactions (DDDIs). Furthermore, the pronounced inter-individual variability in PK observed in ESRD patients highlights the urgent need for individualized PBPK models. Methods: In this study, we developed a PBPK population model for ESRD patients, incorporating functional changes in key drug-metabolizing enzymes and transporters (DMETs), including CYP3A4, OATP1B1/3, P-gp, and BCRP. The model was initially constructed using the recalibrated demographic and physiological parameters of ESRD patients. Then, we used five well-validated substrates (midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin) and their corresponding PK profiles from ESRD patients taking a microdose cocktail regimen to simultaneously estimate the abundance of all these DMETs. Lastly, machine learning was employed to identify potential factors influencing individual clearance. Results: Our study suggested a significant reduction in hepatic OATP1B1/3 (75%) and intestinal P-gp abundance (34%) in ESRD patients. Ileum BCRP abundance was estimated to increase by 100%, while change in hepatic CYP3A4 abundance is minimal. Notably, simulations of drug combinations revealed potential DDDI risks that were not observed in healthy volunteers. Machine learning further identified Clostridium XVIII and Escherichia genus abundances as significant factors influencing dabigatran clearance. For rosuvastatin, aspartate aminotransferase, total bilirubin, Bacteroides, and Megamonas genus abundances were key influencers. No significant factors were identified for midazolam, pitavastatin, or atorvastatin. Conclusions: Our study proposes a feasible strategy for individualized PK prediction by integrating PBPK modeling with machine learning to support the development and precise use of the aforementioned DMET substrates in ESRD patients. Full article
(This article belongs to the Special Issue Recent Advances in Physiologically Based Pharmacokinetics)
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30 pages, 4270 KiB  
Review
Latest Advances in Inhalable Dry Powder Bacteriophage Therapy for Pulmonary Infections
by David Encinas-Basurto, Patricia Dolores Martinez-Flores, Joselyn García, Marco Antonio Lopez-Mata, Gerardo García-González, Gerardo E. Rodea, Basanth Babu Eedara, Heidi M. Mansour and Josue Juarez
Pharmaceutics 2025, 17(8), 1077; https://doi.org/10.3390/pharmaceutics17081077 - 20 Aug 2025
Viewed by 172
Abstract
The concerning increase in respiratory infections that are resistant to multiple drugs has led to a growing interest in bacteriophage therapy as a potential alternative to conventional antibiotics. Effective phage delivery to the lungs, however, presents several formulation and stability issues, particularly for [...] Read more.
The concerning increase in respiratory infections that are resistant to multiple drugs has led to a growing interest in bacteriophage therapy as a potential alternative to conventional antibiotics. Effective phage delivery to the lungs, however, presents several formulation and stability issues, particularly for inhalation-based methods. This review highlights current developments in the creation of dry powder formulations that can be inhaled for pulmonary phage therapy, with a focus on encapsulation methods based on nanoparticles, such as solid lipid nanoparticles (SLNs) and polymer-based nanoparticles. These carriers enhance the aerodynamic characteristics of phages, making them suitable for deep lung deposition, while also protecting them during processing and storage. Several drying methods have been investigated to create powders with optimal morphologies, porosity, and dispersibility, including spray drying and spray freeze drying. The review also emphasizes how the phage morphotype affects stability, especially when nebulization stress is present. Furthermore, the advantages of nanoparticle matrices are confirmed by the reduced viability loss (usually< 0.5 log PFU) of encapsulated phages. Standardizing production processes, scaling up, and ensuring regulatory compliance remain challenging despite encouraging preclinical results. The combination of phage therapy with nanotechnology creates new avenues for the utilization of inhalable delivery methods to treat multidrug-resistant pulmonary infections. To translate these novel formulations from preclinical development to clinical application, sustained multidisciplinary collaboration across pharmaceutical sciences, microbiology, and clinical pharmacology is essential. Full article
(This article belongs to the Special Issue Development and Evaluation of Inhalable Dry Powder Formulations, 2nd Edition)
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24 pages, 4059 KiB  
Article
Nanostructured Lipid Carriers for Sustained Release and Enhanced Delivery of Vanda coerulea Protocorm Extract
by Piyatida Amnuaykan, Pimporn Anantaworasakul, Kodpaka Lueadnakrob, Pongsagon Kunkul, Wilasinee Chokrungsarid, Aiya Thummanuwong, Saranya Juntrapirom, Watchara Kanjanakawinkul and Wantida Chaiyana
Pharmaceutics 2025, 17(8), 1076; https://doi.org/10.3390/pharmaceutics17081076 - 20 Aug 2025
Viewed by 225
Abstract
Background/Objectives: This study aimed to develop a nanostructured lipid carrier (NLC) system incorporating a catechin-rich Vanda coerulea extract for topical cosmetic applications and to evaluate its physicochemical properties, release behavior, and skin retention performance. Methods: Blank NLCs were prepared using hot emulsification followed [...] Read more.
Background/Objectives: This study aimed to develop a nanostructured lipid carrier (NLC) system incorporating a catechin-rich Vanda coerulea extract for topical cosmetic applications and to evaluate its physicochemical properties, release behavior, and skin retention performance. Methods: Blank NLCs were prepared using hot emulsification followed by sonication, with glyceryl monostearate, caprylic triglyceride, Poloxamer® 188, and Tween® 80 as the formulation components. NLCs with varying solid-to-liquid lipid ratios were developed while maintaining a constant total lipid content of 5% w/w. The formulations were characterized based on their particle size, polydispersity index (PDI), zeta potential, and physical stability, including stability after a heating–cooling cycle test. The effect of ultrasonication duration was also evaluated. The optimized NLC was then loaded with a V. coerulea extract and evaluated for in vitro release and skin retention using catechin as a marker. Results: The NLC with a particle size of 235.5 ± 29.8 nm, a narrow PDI range of 0.382 ± 0.090, and a strong zeta potential of −29.8 ± 0.3 mV was selected for the incorporation of the V. coerulea extract. The extract-loaded NLC exhibited a sustained release over 24 h, significantly different from the V. coerulea extract solution (p < 0.05). Skin retention studies revealed that the NLC achieved approximately twice the catechin retention compared to the solution at the 1 h time point (1.30 ± 0.01% vs. 0.68 ± 0.03% w/w). Conclusions: The V. coerulea-extract-loaded NLC demonstrated favorable physicochemical properties, sustained release behavior, and enhanced skin retention. These findings support its potential as a promising topical delivery system for antioxidant-rich botanical extracts in cosmetic applications. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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18 pages, 1464 KiB  
Article
Killer Peptide-Containing Polyelectrolytic Nanocomplexes to Fight Toxoplasma gondii Infection
by Arianna Bucella, Manuela Semeraro, Laura Giovati, Lorenza Artesani, Ruggero Bettini, Annalisa Bianchera and Alice Vismarra
Pharmaceutics 2025, 17(8), 1075; https://doi.org/10.3390/pharmaceutics17081075 - 20 Aug 2025
Viewed by 192
Abstract
Background/Objectives: Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, typically is asymptomatic in immunocompetent individuals but causes severe complications in immunocompromised subjects and during pregnancy. Current treatments such as pyrimethamine and sulfadiazine are effective for acute infections but cannot eliminate encysted bradyzoites [...] Read more.
Background/Objectives: Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, typically is asymptomatic in immunocompetent individuals but causes severe complications in immunocompromised subjects and during pregnancy. Current treatments such as pyrimethamine and sulfadiazine are effective for acute infections but cannot eliminate encysted bradyzoites and have significant side effects. The antimicrobial killer peptide (KP) has interesting therapeutic potential, but its intracellular delivery is challenging; hyaluronate-based nanoparticles loaded with KP (KP-NPs) were evaluated to target T. gondii-infected cells that overexpress CD44. Methods: KP-NPs made of chitosan and hyaluronate were produced by microfluidics and were characterized for size, surface charge, encapsulation efficiency, and stability under stress conditions. After excluding their toxicity, their activity was tested in vitro against Candida albicans and T. gondii as free tachyzoite or in infected human foreskin fibroblasts (HFFs). Results: KP was efficiently encapsulated in nanoparticles and protected from harsh acidic conditions at high temperature. Preliminary in vitro testing against C. albicans showed that, at the lowest candidacidal concentration of KP (2.5 μg/mL), KP-NPs killed 90.97% of yeast cells. KP itself proved to be non-toxic for HFFs as host cells and effective against T. gondii. Comparable results were obtained for KP-NPs and blank nanoparticles (BLK-NPs), with no observed toxicity to host cells, confirming that encapsulation did not alter peptide efficacy. The parasiticidal effect of KP alone, as well as KP-NPs at 250 µg/mL and BLK-NPs, was confirmed through tests on free T. gondii tachyzoites. Reduction rates for the number of infected cells ranged from 66% to 90% with respect to control, while the reduction in the number of intracellular tachyzoites ranged from 66% to 80%. Interestingly, KP alone was not effective against intracellular tachyzoite, while KP-NPs maintained an efficacy comparable to the extracellular model, suggesting that particles helped the internalization of the peptide. Conclusions: Encapsulation of KP into hyaluronate/chitosan nanoparticles does not alter its activity and improves its efficacy against the intracellular parasite. Notably, BLK-NPs appeared to exhibit efficacy against the parasite on its own, without the presence of KP. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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22 pages, 1359 KiB  
Review
Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization
by Shujun Fu, Xueran Zhu, Fanghua Huang and Xiaoyan Chen
Pharmaceutics 2025, 17(8), 1074; https://doi.org/10.3390/pharmaceutics17081074 - 20 Aug 2025
Viewed by 260
Abstract
Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may result in toxicity due to PEG accumulation in tissues, leading to the formation of anti-PEG antibodies (APAs), which [...] Read more.
Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may result in toxicity due to PEG accumulation in tissues, leading to the formation of anti-PEG antibodies (APAs), which can accelerate drug clearance, reduce efficacy, and alongside enhanced side effects, such as allergic reactions. Notably, pre-existing APAs have also been detected in individuals with no prior exposure to PEGylated drugs, raising additional clinical concerns. This review summarizes the mechanisms of APA generation, the factors influencing PEG immunogenicity, and the biological consequences of APAs on drug pharmacokinetics, efficacy, and safety. We also discuss current challenges in APA detection and highlight strategies to minimize immunogenic responses, including PEG modification, immunomodulation, and alternative polymers. This review aims to provide a comprehensive reference for the rational design, evaluation, and clinical management of PEGylated drugs. Full article
(This article belongs to the Section Biopharmaceutics)
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30 pages, 449 KiB  
Review
Sublingual and Buccal Delivery: A Historical and Scientific Prescriptive
by Sina Bahraminejad and Hassan Almoazen
Pharmaceutics 2025, 17(8), 1073; https://doi.org/10.3390/pharmaceutics17081073 - 20 Aug 2025
Viewed by 450
Abstract
In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 [...] Read more.
In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 and 2025. The early phase of sublingual and buccal drug delivery (1950–1982) saw limited attempts to explore this delivery route. The exploratory growth phase (1983–1993) was marked by the use of nitroglycerin to treat angina, calcium channel blockers to treat hypertension, ACE inhibitors to treat heart conditions, the use of opioids in pain management therapy, and peptide and hormonal therapy. The diversification and discovery phase (1994–2009) was marked by the introduction of small molecules for the treatment of opioid use disorder and analgesia, the use of animal models to enhance the pharmacokinetic understanding of the sublingual and buccal route, the use of penetration enhancers, peptide and hormonal therapy, and few marked FDA drug approvals in this area. The innovation and integration phase (2010–2025) was marked by the use of nanoparticles, multilayered mucoadhesive systems, pediatric formulations (fast-dissolving films and tablets), immunotherapy and vaccine delivery, and a broad spectrum of therapeutic agents, such as steroids, antifungals, cannabinoids, antidepressants, antipsychotics, and narcotics (e.g., buprenorphine and apomorphine), novel formulations of fentanyl and diazepam for pain and seizure control, and the introduction of buccal vitamin D3 sprays. Understanding the history of sublingual and buccal delivery demonstrates a growing area of research focused on enhancing mucosal drug delivery for achieving local and systemic therapeutic benefits. Full article
(This article belongs to the Special Issue Advanced Strategies for Sublingual and Buccal Drug Delivery)
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1 pages, 135 KiB  
Correction
Correction: Andjic et al. Immortelle Essential-Oil-Enriched Hydrogel for Diabetic Wound Repair: Development, Characterization, and In Vivo Efficacy Assessment. Pharmaceutics 2024, 16, 1309
by Marijana Andjic, Jovana Bradic, Aleksandar Kocovic, Marko Simic, Veljko Krstonosic, Ivan Capo, Vladimir Jakovljevic and Nevena Lazarevic
Pharmaceutics 2025, 17(8), 1072; https://doi.org/10.3390/pharmaceutics17081072 - 19 Aug 2025
Viewed by 173
Abstract
In the original publication [...] Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
23 pages, 5631 KiB  
Article
Obtention and Characterization of TiO2-Folic Acid-ZnPc Semiconductor Nanoparticles for Photodynamic Therapy Against Glioma Cells
by Citlali Ekaterina Rodríguez-Pérez, Sonia Rodríguez-García, Ma. Elena Manríquez-Ramírez, A. Martin Ortiz-Torres, Francisco Tzompantzi-Morales and Emma Ortiz-Islas
Pharmaceutics 2025, 17(8), 1071; https://doi.org/10.3390/pharmaceutics17081071 - 19 Aug 2025
Viewed by 242
Abstract
Background/Objectives: This study reports the synthesis of TiO2 nanoparticles, their functionalization with folic acid (FA), and the subsequent loading with zinc phthalocyanine (ZnPc) to develop photosensitizers for photodynamic therapy (PDT) targeting glioma cells. Methods: TiO2, TiO2-FA, and TiO [...] Read more.
Background/Objectives: This study reports the synthesis of TiO2 nanoparticles, their functionalization with folic acid (FA), and the subsequent loading with zinc phthalocyanine (ZnPc) to develop photosensitizers for photodynamic therapy (PDT) targeting glioma cells. Methods: TiO2, TiO2-FA, and TiO2-FA-ZnPc nanoparticles were synthesized via a sol–gel process involving the hydrolysis and condensation of titanium (IV) isopropoxide. FA and ZnPc were incorporated in vitro during the synthesis. The resulting materials were characterized by transmission and scanning electron microscopy (TEM and SEM), X-ray diffraction (XRD), Raman and UV–Vis spectroscopy, thermogravimetric analysis (TGA), and nitrogen adsorption–desorption measurements. Reactive oxygen species (ROS) generation was evaluated in vitro using the 1,3-diphenylisobenzofuran (DPBF) probe. A 40 ppm solution of each TiO2 system was irradiated with UV light, and the degradation of DPBF was monitored. Biological assays were conducted to assess the viability of human glioblastoma cells (LN18 and U251) incubated with the TiO2-based materials, with and without UV exposure. Human fibroblast cells (BJ) were used to evaluate biocompatibility. Results: All TiO2-based materials retained key characteristics, including high surface area (~600–700 m2/g), mesoporous structure (pore diameter ~4–5 nm), mixed anatase–amorphous morphology, and a bandgap of approximately 3.46 eV. The UV–Vis spectrum of TiO2-FA-ZnPc displayed additional absorption bands in the visible region (600–700 nm), consistent with ZnPc incorporation. Upon UV irradiation, the DPBF absorbance at 410 nm decreased over time, indicating ROS generation and resulting in complete degradation within 10 min (TiO2), 12 min (TiO2-FA), and 14 min (TiO2-FA-ZnPc). BJ cells exhibited good biocompatibility at all concentrations. LN18 and U251 cells showed no cytotoxicity below 100 μg/mL unless exposed to UV light. Conclusions: The synthesized TiO2-based systems demonstrate good biocompatibility and significant phototoxicity under UV irradiation, highlighting their strong potential for application in photodynamic therapy. Full article
(This article belongs to the Special Issue Innovative Applications of Nanotechnology and Photothermal Therapy in Cancer Treatment and Drug Delivery)
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13 pages, 569 KiB  
Review
Microbiological Impact of Antimicrobial Photodynamic Therapy in Non-Surgical Periodontal Treatment
by Filipa Passos Sousa, Mariana Anselmo Assunção, Lucinda J. Bessa and Ricardo Castro Alves
Pharmaceutics 2025, 17(8), 1070; https://doi.org/10.3390/pharmaceutics17081070 - 19 Aug 2025
Viewed by 226
Abstract
Periodontitis is one of the most common inflammatory diseases and it is linked to the presence of a dysbiotic subgingival microbiome. The purpose of this review is to evaluate the impact of antimicrobial photodynamic therapy (aPDT) on the subgingival microbiome. Herein, based on [...] Read more.
Periodontitis is one of the most common inflammatory diseases and it is linked to the presence of a dysbiotic subgingival microbiome. The purpose of this review is to evaluate the impact of antimicrobial photodynamic therapy (aPDT) on the subgingival microbiome. Herein, based on an extensive evaluation of randomized controlled trials (RCTs), the effects of aPDT as a supplement to non-surgical periodontal therapy (NSPT) were found to be the main focus of these works. Studies that focused on analyzing microbiological results were selected, yielding contradictory results. The observed microbiological changes were variable, even though some studies showed notable improvements in clinical indicators such as bleeding on probing (BOP), clinical attachment level (CAL), and probing depth (PD). Several studies found that aPDT did not significantly reduce important periodontal pathogens such Tannerella forsythia, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. Nevertheless, after multiple aPDT sessions, other studies reported positive changes in the subgingival microbiome, with a rise in beneficial bacteria and a decrease in periodontopathogens. While aPDT seems to be a safe and well-tolerated adjuvant to non-surgical periodontal therapy, there is still conflicting evidence regarding how well it modulates the subgingival microbiota. Additional long-term research with larger sample sizes is required to evaluate the microbiological and clinical advantages of aPDT. Full article
(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research, 2nd Edition)
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24 pages, 4087 KiB  
Article
Significant Improvement in Bioavailability and Therapeutic Efficacy of Mebendazole Oral Nano-Systems Assessed in a Murine Model with Extreme Phenotypes of Susceptibility to Trichinella spiralis
by Ana V. Codina, Paula Indelman, Lucila I. Hinrichsen and María C. Lamas
Pharmaceutics 2025, 17(8), 1069; https://doi.org/10.3390/pharmaceutics17081069 - 19 Aug 2025
Viewed by 280
Abstract
This study aimed to analyze whether the enhancement of the biopharmaceutical efficiency of mebendazole, a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Objectives: Two advanced oral formulations were developed, polyvinyl alcohol-derived nanoparticles (NP) and [...] Read more.
This study aimed to analyze whether the enhancement of the biopharmaceutical efficiency of mebendazole, a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Objectives: Two advanced oral formulations were developed, polyvinyl alcohol-derived nanoparticles (NP) and β-cyclodextrin citrate inclusion complexes (Comp), both employing mebendazole as an anthelmintic agent. The primary objective of this work is to treat trichinellosis, an infection with severe chronic effects. Methods: The physicochemical characteristics as well as the in vivo performance of the NP and Comp formulations were assessed. The in vivo studies involved the bioavailability analysis, comparing drug absorption between the pure drug and the novel formulations, as well as the in vitro anthelmintic activity and in vivo therapeutic efficacy against Trichinella spiralis encysted muscle larvae. The in vivo efficacy was evaluated during the parenteral stage of T. spiralis infection in male and female mice from two genetically distinct lines differing in mebendazole pharmacokinetic parameters and susceptibility to the parasite. Results: The formulations exhibited smaller particle sizes and improved dissolution properties compared to pure MBZ. The pharmacokinetics studies indicate that NP and Comp significantly improved MBZ bioavailability. Both NP and Comp significantly increased mebendazole’s anthelmintic activity against the encysted parasites, which would be attributed to the improved MBZ absorption. The formulations overcome the drug’s poor solubility and low bioavailability limitations, resulting in a higher plasma concentration of the active drug, even at low doses. Conclusions: These findings suggest that the newly designed mebendazole formulations are suitable for treating T. spiralis chronic infection and highlight a potential improvement in the pharmacological treatment of trichinellosis. Full article
(This article belongs to the Special Issue Advanced Nano-Based Drug Delivery Systems for Infectious Diseases)
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28 pages, 1547 KiB  
Review
Chitosan Nanoparticles Loaded with Polyphenols for Cosmeceutical Applications: A State-of-the-Art Review
by Valeria Gaetano, Agnese Gagliardi, Elena Giuliano, Emanuela Longo and Donato Cosco
Pharmaceutics 2025, 17(8), 1068; https://doi.org/10.3390/pharmaceutics17081068 - 18 Aug 2025
Viewed by 257
Abstract
Nanotechnology has been widely employed in the field of cosmeceuticals, promoting the development of innovative cosmetic formulations characterized by notable pharmacological activity. The use of nanocosmeceuticals allows for better skin penetration of active compounds, their controlled release over time, and greater physico-chemical stability. [...] Read more.
Nanotechnology has been widely employed in the field of cosmeceuticals, promoting the development of innovative cosmetic formulations characterized by notable pharmacological activity. The use of nanocosmeceuticals allows for better skin penetration of active compounds, their controlled release over time, and greater physico-chemical stability. Chitosan nanoparticles have generated significant interest in the scientific community as dermal and transdermal delivery systems for natural compounds. In particular, the encapsulation of polyphenols within chitosan nanosystems has been proposed as a method to enhance the effectiveness of bioactives in cosmeceutical formulations. This review discusses the most relevant scientific literature on the topic, with particular attention to studies published in recent years. Chitosan-based nanosystems improve the stability, bioavailability, and skin compatibility of polyphenols, offering promising solutions for the prevention and treatment of skin disorders due to their antioxidant and anti-inflammatory properties. This review provides a comprehensive update on the development of chitosan nanoparticles containing polyphenols and their potential clinical applications, highlighting the role of these systems as nanocosmeceuticals. Full article
(This article belongs to the Special Issue Methods of Potentially Improving Drug Permeation and Bioavailability)
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17 pages, 965 KiB  
Article
Use of Factorial Designs to Reduce Stability Studies for Parenteral Drug Products: Determination of Factor Effects via Accelerated Stability Data Analysis
by Lara Pavčnik, Simona Bohanec, Tina Trdan Lušin and Robert Roškar
Pharmaceutics 2025, 17(8), 1067; https://doi.org/10.3390/pharmaceutics17081067 - 18 Aug 2025
Viewed by 279
Abstract
Objectives: This study explores the potential of factorial analysis as an alternative strategy for optimizing stability study designs for registration batches—an approach not currently addressed in ICH Q1D, which focuses solely on bracketing and matrixing. The objective is to assess the reliability of [...] Read more.
Objectives: This study explores the potential of factorial analysis as an alternative strategy for optimizing stability study designs for registration batches—an approach not currently addressed in ICH Q1D, which focuses solely on bracketing and matrixing. The objective is to assess the reliability of stability designs reduced based on factorial analysis and the extent to which long-term stability testing can be reduced using this approach. Methods: To determine the feasibility of applying factorial analysis for stability study design reduction while preserving the reliability of stability assessments, three parenteral dosage forms were selected. Stability data under both accelerated and long-term storage conditions were analyzed. Factorial analysis was applied to the accelerated data to identify critical factors influencing stability (e.g., filling volume, orientation). Based on these findings, long-term study designs were strategically reduced, and the validity of these reductions was confirmed through regression analysis of long-term data. Results: Factorial analysis revealed key factors significantly affecting stability, including batch, orientation, filling volume, and drug substance supplier. The analysis identified the worst-case scenarios and, based on this, proposed a drastic reduction in the long-term stability study designs for three tested parenteral drug products. The regression analysis results confirmed the usefulness of factorial analysis for the reduction of long-term stability testing of tested parenteral drug products for at least 50%. Conclusions: This study demonstrates that factorial analysis of accelerated stability data is a valuable tool for optimizing long-term stability study designs for parenteral pharmaceutical dosage forms. The findings suggest that this approach could complement existing ICH Q1D strategies, offering the pharmaceutical industry a scientifically sound method to streamline stability programs, reduce costs, and accelerate development timelines while maintaining product quality, safety, and efficacy. Full article
(This article belongs to the Special Issue Stability of Medicines and Novel Approaches for Predicting Drug Stability)
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17 pages, 1880 KiB  
Article
Dual-Phase Ocular Insert with Bromfenac-Loaded PLGA MPs in a PVA Matrix for Sustained Postoperative Anti-Inflammatory Delivery
by Farhan Alshammari, Bushra Alshammari, Asma Khalaf Alshamari, Kaushik Sarkar and Raghu Raj Singh Thakur
Pharmaceutics 2025, 17(8), 1066; https://doi.org/10.3390/pharmaceutics17081066 - 17 Aug 2025
Viewed by 494
Abstract
Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study [...] Read more.
Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (w/w) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. Methods: PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and t-tests with p < 0.05 as significance. Results: MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7–8% and entrapment efficiencies 47–52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). Conclusions: The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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19 pages, 2030 KiB  
Article
Population Pharmacokinetics of Tideglusib in Congenital and Childhood Myotonic Dystrophy Type 1: Influence of Demographic and Clinical Factors on Systemic Exposure
by Alessandro Di Deo, Sean Oosterholt, Joseph Horrigan, Stuart Evans, Alison McMorn and Oscar Della Pasqua
Pharmaceutics 2025, 17(8), 1065; https://doi.org/10.3390/pharmaceutics17081065 - 16 Aug 2025
Viewed by 315
Abstract
Background: GSK3β is an intracellular regulatory kinase that is dysregulated in multiple tissues in Type 1 myotonic dystrophy (DM-1). Tideglusib inhibits GSK3β activity in preclinical models of DM-1 and promotes cellular maturation, normalising aberrant molecular and behavioural phenotypes. It is currently in [...] Read more.
Background: GSK3β is an intracellular regulatory kinase that is dysregulated in multiple tissues in Type 1 myotonic dystrophy (DM-1). Tideglusib inhibits GSK3β activity in preclinical models of DM-1 and promotes cellular maturation, normalising aberrant molecular and behavioural phenotypes. It is currently in clinical development for the treatment of paediatric and adult patients affected by congenital and juvenile-onset DM-1. Here, we summarise the development of a population pharmacokinetic model and subsequent characterisation of influential demographic and clinical factors on the systemic exposure to tideglusib. The availability of a population PK model will allow further evaluation of age-and weight-related changes in drug disposition, supporting the dose rationale and implementation of a paediatric extrapolation plan. Methods: Given the sparse pharmacokinetic sampling scheme in patients receiving tideglusib, model development was implemented in two steps. First, data from Phase I studies in healthy elderly subjects (i.e., 1832 plasma samples, n = 54) were used to describe the population pharmacokinetics of tideglusib in adults. Then, pharmacokinetic model parameter estimates obtained from healthy subjects were used as priors for the evaluation of the disposition of tideglusib in adolescent and adult DM-1 patients (51 plasma samples, n = 16), taking into account demographic and clinical baseline characteristics, as well as food intake. Secondary pharmacokinetic parameters (AUC, Cmax and Tmax) were derived and summarised by descriptive statistics. Results: Tideglusib pharmacokinetics was described by a two-compartment model with first-order elimination and dose-dependent bioavailability. There were no significant differences in disposition parameters between healthy subjects and DM-1 patients. Body weight was a significant covariate on clearance and volume of distribution. Median AUC(0–12) and Cmax were 1218.1 vs. 3145.7 ng/mL∙h and 513.5 vs. 1170.9 ng/mL, following once daily doses of 400 and 1000 mg tideglusib, respectively. In addition, the time of food intake post-dose or the type of meal appeared to affect the overall exposure to tideglusib. No accumulation, metabolic inhibition, or induction was observed during the treatment period. Conclusions: Even though clearance was constant over the dose range between 400 and 1000 mg, a less than proportional increase in systemic exposure appears to be caused by the dose-dependent bioavailability, which reflects the solubility properties of tideglusib. Despite large interindividual variability in the tideglusib concentration vs. time profiles, body weight was the only explanatory covariate for the observed differences. This finding suggests that the use of weight-banded or weight-normalised doses should be considered to ensure comparable exposure across the paediatric population, regardless of age or body weight. Full article
(This article belongs to the Special Issue Population Pharmacokinetics and Its Clinical Applications)
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16 pages, 512 KiB  
Review
The Role of PEDF in the Eye, Bone, and Nervous and Immune Systems
by Krittikan Chanpaisaeng and Crispin R. Dass
Pharmaceutics 2025, 17(8), 1064; https://doi.org/10.3390/pharmaceutics17081064 - 15 Aug 2025
Viewed by 420
Abstract
This review highlights recent findings on the versatile inactive serpin protein, pigment epithelium-derived factor (PEDF) in the eye, bone, and nervous and immune systems. PEDF is highly conserved and found at the 17p13.3 locus in humans. PEDF initially discovered in the eye, also [...] Read more.
This review highlights recent findings on the versatile inactive serpin protein, pigment epithelium-derived factor (PEDF) in the eye, bone, and nervous and immune systems. PEDF is highly conserved and found at the 17p13.3 locus in humans. PEDF initially discovered in the eye, also has critical roles in the bone including de novo bone regeneration. It is also involved in the nervous system, with roles in such widespread and increasing-in-prevalence conditions such as depression, orchestrating the immune system, coordinating immune cells, and warding off disease. This manuscript comprehensively reviews the protein, listing a majority of all the publicly available studies reported, to date, in these four separate body systems. It thus showcases PEDF’s versatility in the human body. It also highlights the applicability of PEDF peptides, shorter in length, and in some cases just as potent as the parent protein in these discussed ailments. Full article
(This article belongs to the Section Biologics and Biosimilars)
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19 pages, 5085 KiB  
Article
Fabrication and Evaluation of Isomalt-Based Microfibers as Drug Carrier Systems
by Andrea Kovács, Bálint Attila Kecskés, Gábor Filipszki, Dóra Farkas, Bence Tóth, István Antal and Nikolett Kállai-Szabó
Pharmaceutics 2025, 17(8), 1063; https://doi.org/10.3390/pharmaceutics17081063 - 15 Aug 2025
Viewed by 394
Abstract
Background/Objectives: The melt-spinning process has seen limited application in the pharmaceutical industry. However, nano- and microfibrous structures show significant potential for novel drug delivery systems, due to their high specific surface area. To facilitate broader adoption in pharmaceutical technology, critical parameters influencing [...] Read more.
Background/Objectives: The melt-spinning process has seen limited application in the pharmaceutical industry. However, nano- and microfibrous structures show significant potential for novel drug delivery systems, due to their high specific surface area. To facilitate broader adoption in pharmaceutical technology, critical parameters influencing fiber quality and yield must be investigated. In this study, we aimed to develop an isomalt-based microfibrous carrier system for active pharmaceutical ingredients. Methods: The effects of different isomalt compositions—specifically, varying ratios of GPS (6-O-α-d-glucopyranosyl-d-sorbitol) and GPM (1-O-α-d-glucopyranosyl-d-mannitol)—as well as key process parameters, were systematically investigated to optimize fiber formation. The prepared fibers underwent different treatments. Morphological changes were monitored with a microscope, and microstructural changes were studied using a differential scanning calorimeter and X-ray diffractometer. The macroscopic behavior of the fibers was evaluated by image analysis under monitored conditions. Results: Statistical analysis was used to determine the optimal setting to produce isomalt-based fibers. We found that storage over ethanol vapor has a positive effect on the stability of the fibers. We successfully prepared ibuprofen sodium-containing fibers that remained stable after alcohol treatment and enabled drug release within 15 s. Conclusions: It was found that the applied GPS:GPM isomalt ratio significantly influenced fiber formation and that storage over ethanol positively influenced the processability and stability of the fibrous structure. An isomalt-based microfibrous system with advantageous physicochemical and structural properties was successfully developed as a potential drug carrier. The system is also resistant to the destructive effects of ambient humidity, enabling preparation of suitable dosage forms. Full article
(This article belongs to the Special Issue Advancements in Tablet Formulation and Technological Innovations in Pharmaceutical Manufacturing)
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32 pages, 3378 KiB  
Review
Thermoresponsive and Fluorescent Polymers: From Nanothermometers to Smart Drug Delivery Systems for Theranostics Against Cancer
by Mirian A. González-Ayón, Jesús E. Márquez-Castro, Diana V. Félix-Alcalá and Angel Licea-Claverie
Pharmaceutics 2025, 17(8), 1062; https://doi.org/10.3390/pharmaceutics17081062 - 15 Aug 2025
Viewed by 583
Abstract
This mini-review article is focused on polymeric materials that comprise thermoresponsive and fluorescent organic units. The combination of fluorescent clusters/dots embedded in or grafted with polymers is not considered in this article. Here we review the preparation, characterization, and application of thermoresponsive polymers [...] Read more.
This mini-review article is focused on polymeric materials that comprise thermoresponsive and fluorescent organic units. The combination of fluorescent clusters/dots embedded in or grafted with polymers is not considered in this article. Here we review the preparation, characterization, and application of thermoresponsive polymers functionalized covalently with organic fluorescent compounds either compartmentalized or randomly distributed: block-copolymers, self-assembled micelles or vesicles, core–shell nanogels, and their temperature driven self-assembly/shrinkage/expansion and resulting effect in fluorescence: quenching, enhancing, shifting. The applications suggested for these smart-materials are reviewed in the last ten years and range from nanothermometers, drug delivery systems, agents for bioimaging, sensors, and advanced materials for theranostics focused on cancer treatment. This article is organized reviewing the preparation methods, the main characterization techniques, and the application, depending on polymer architecture and the emission wavelength of the fluorophores. Finally, comments, suggestions, and problems to be solved for the advancement of these materials in the future prior to real-life applications are given. Full article
(This article belongs to the Special Issue Functionalized Polymers for Anticancer Applications)
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18 pages, 1286 KiB  
Article
Oral Delivery of Avocado Peel Extract Using Albumin Nanocarriers to Modulate Cholesterol Absorption
by Laura M. Teixeira, Ana S. Viana, Catarina P. Reis and Rita Pacheco
Pharmaceutics 2025, 17(8), 1061; https://doi.org/10.3390/pharmaceutics17081061 - 15 Aug 2025
Viewed by 359
Abstract
Background/Objectives: Hypercholesterolemia, a metabolic disorder and major risk factor for cardiovascular disease, remains a global health concern. Although current pharmacological interventions effectively reduce cholesterol levels, their use is often associated with adverse side effects. These limitations have driven interest in alternative or complementary [...] Read more.
Background/Objectives: Hypercholesterolemia, a metabolic disorder and major risk factor for cardiovascular disease, remains a global health concern. Although current pharmacological interventions effectively reduce cholesterol levels, their use is often associated with adverse side effects. These limitations have driven interest in alternative or complementary approaches based on natural products; however, the poor solubility, stability, and bioavailability of many natural compounds emphasize the need for innovative drug delivery systems to enhance their health-promoting potential. The extract obtained from Persea americana peels, a sustainable and underutilized by-product, has previously been reported to have cholesterol-lowering properties. Methods: The extract was encapsulated in bovine serum albumin nanoparticles. The nanoformulation was characterized for physicochemical properties and for extract stability under acid-simulated gastric digestion. Safety and biocompatibility were evaluated by in vitro cytotoxicity assays using intestinal Caco-2 and liver HepG2 cells, and in vivo toxicity using Artemia salina. The bioavailability of the extract and the nanoformulation’s capacity to reduce cholesterol absorption in a differentiated Caco-2 cell model were additionally assessed. Results: Encapsulation enhanced extract stability and bioavailability, protecting it from degradation in acid simulated gastric digestion. The nanoparticles showed favorable physicochemical properties, including a small size of less than 100 nm, and demonstrated safety and biocompatibility. In the Caco-2 model, the encapsulation of the extract resulted in reduced cholesterol permeation compared to the free extract Conclusions: These findings suggest that the nanoformulation developed may offer a safe and effective strategy for the oral delivery of P. americana peel extract, reinforcing its potential for application in hypercholesterolemia management. Full article
(This article belongs to the Special Issue Advances in Drug Delivery Systems for the Management of Metabolic Diseases)
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25 pages, 1441 KiB  
Review
Nanocarriers in Ungual Drug Delivery
by Sheila Porto de Matos, Karen de Oliveira Araujo, Tainá Kreutz, Valdir Florêncio da Veiga Júnior, Helder Ferreira Teixeira and Letícia Scherer Koester
Pharmaceutics 2025, 17(8), 1060; https://doi.org/10.3390/pharmaceutics17081060 - 15 Aug 2025
Viewed by 405
Abstract
Ungual disorders can impact quality of life, with onychomycosis and nail psoriasis being the most prevalent disorders among the general population. In humans, the main functions of the nail apparatus comprise protection against trauma, improvement of tactile sensations, and allowing precision gripping. In [...] Read more.
Ungual disorders can impact quality of life, with onychomycosis and nail psoriasis being the most prevalent disorders among the general population. In humans, the main functions of the nail apparatus comprise protection against trauma, improvement of tactile sensations, and allowing precision gripping. In order to perform such functions, the nail plate has a hard structure formed by dead keratinized corneocytes tightly bound to each other, giving the nail plate a “barrier-like” character. Due to this property of the nail plate, drug delivery to the region is hindered, making the treatment of ungual disorders difficult, either by systemic or topical drug administration. Many strategies have been developed in the last few decades in an attempt to increase the bioavailability of drugs in the nail. Interest in the employment of nanostructured drug delivery systems aiming to increase the bioavailability of drugs in the nail plate upon topical administration has increased. Moreover, the association of the nanotechnological approaches with other methods may be a beneficial strategy when aiming to increase drug permeation through the nail barrier. In this sense, the present review has the intention of presenting the panorama of the current technological development of nanostructured systems designed for the local treatment of ungual disorders. Through this extensive literature review, it was possible to recognize, among the studies, a lack of standardization regarding the methodology of nail permeation assessment, which imposes an obstacle to comparison. Full article
(This article belongs to the Special Issue Innovations in Ungual and Dermal Drug Delivery Systems for Localized Therapies)
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3 pages, 864 KiB  
Correction
Correction: Koush et al. Chitosan-Stabilized Lipid Vesicles with Indomethacin for Modified Release with Prolonged Analgesic Effect: Biocompatibility, Pharmacokinetics and Organ Protection Efficacy. Pharmaceutics 2025, 17, 523
by Angy Abu Koush, Eliza Gratiela Popa, Beatrice Rozalina Buca, Cosmin Gabriel Tartau, Iulian Stoleriu, Ana-Maria Raluca Pauna, Liliana Lacramioara Pavel, Paula Alina Fotache and Liliana Mititelu Tartau
Pharmaceutics 2025, 17(8), 1059; https://doi.org/10.3390/pharmaceutics17081059 - 15 Aug 2025
Viewed by 246
Abstract
In the original publication [...] Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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