Pharmaceutics

37 pages, 7351 KB

Open AccessReview

Metal Nanoparticle-Reinforced Hydrogels Applied in the Inhibition of Clinical Pathogens: Structural Features, Mechanisms, and Biomedical Prospects

by Lizeth Geraldine Muñoz, Yhors Ciro and Andrés Felipe Chamorro

Pharmaceutics 2026, 18(6), 765; https://doi.org/10.3390/pharmaceutics18060765 - 22 Jun 2026

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Abstract

The increasing prevalence of antimicrobial resistance (AMR) has promoted the development of advanced biomaterials capable of overcoming the limitations of conventional antibiotics. In this context, metal nanoparticle hybrid hydrogels (MNHHs) have emerged as multifunctional platforms that integrate the high water-retention capacity and biocompatibility [...] Read more.

The increasing prevalence of antimicrobial resistance (AMR) has promoted the development of advanced biomaterials capable of overcoming the limitations of conventional antibiotics. In this context, metal nanoparticle hybrid hydrogels (MNHHs) have emerged as multifunctional platforms that integrate the high water-retention capacity and biocompatibility of hydrogels with the antimicrobial properties of metallic nanoparticles (MNPs). This review critically analyzes recent advances in the design, physicochemical properties, antimicrobial mechanisms, and biomedical applications of these systems. Current evidence demonstrates that MNHHs can achieve antimicrobial efficiencies above 98–99%, with minimum inhibitory concentrations as low as 0.78 µg mL⁻¹ and inhibition zones of up to 25 mm against clinically relevant pathogens. Furthermore, the incorporation of MNPs significantly improves the mechanical properties of hydrogels and enables controlled and sustained metal ion release for periods of up to 14 days. Despite these promising results, important challenges remain regarding cytotoxicity, release control, the lack of experimental standardization, and the limited understanding of long-term biological effects. Overall, MNHHs represent a promising strategy for infection control, regenerative medicine, and controlled drug delivery; however, their clinical translation still requires the development of reproducible, safe, scalable, and highly biocompatible systems. Full article

(This article belongs to the Special Issue Smart Hydrogels for Drug Delivery Systems and Precision Medicine)

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47 pages, 2613 KB

Open AccessReview

Artificial Intelligence in Nanopharmaceutical Development: From Predictive Design to Clinical Translation

by Renato Sonchini Gonçalves

Pharmaceutics 2026, 18(6), 764; https://doi.org/10.3390/pharmaceutics18060764 - 22 Jun 2026

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Abstract

Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic [...] Read more.

Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic performance. In this review, we examine how AI can contribute to nanopharmaceutical development from predictive formulation design to clinical translation. We synthesize current applications of machine learning, deep learning, physics-informed modeling, hybrid mechanistic–AI approaches, and automated optimization workflows, with emphasis on critical quality attribute modeling, multi-objective optimization, design of experiments, quality-by-design, process analytical technology, digital twins, and continuous manufacturing. We also discuss applications involving nano–bio interactions, pharmacokinetics, toxicity, immunogenicity, and precision nanomedicine. AI-based approaches can support rational nanocarrier design, identify nonlinear formulation–property relationships, guide optimization, improve process understanding, and integrate heterogeneous experimental, biological, and manufacturing datasets across diverse nanopharmaceutical platforms. These methods are particularly relevant for modeling protein corona formation, cellular uptake, intracellular trafficking, biodistribution, pharmacokinetics, toxicity, immunogenicity, and patient-specific responses. However, translational implementation remains limited by fragmented datasets, inconsistent reporting standards, limited interpretability, insufficient external validation, uncertain predictions, poorly defined applicability domains, and evolving regulatory expectations for adaptive computational models. Overall, AI should be viewed not only as an optimization tool, but also as a translational framework connecting formulation science, biological prediction, manufacturing control, and clinical implementation. Future progress will depend on standardized data infrastructures, explainable and externally validated models, uncertainty quantification, applicability-domain definition, hybrid mechanistic–AI frameworks, regulatory-ready documentation, and clinically relevant case studies. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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19 pages, 14810 KB

Open AccessArticle

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Cipepofol Across Diverse Clinical Populations

by Junmin Li, Longjie Li, Fangbin Ding, Meixia Chen, Mengyue Hu, Xiaoqiang Xiang and Jing Tang

Pharmaceutics 2026, 18(6), 763; https://doi.org/10.3390/pharmaceutics18060763 - 22 Jun 2026

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Abstract

Background/Objectives: Cipepofol is a novel intravenous anesthetic whose pharmacokinetics (PK) may vary with dosing regimens, sampling sites, and physiological differences across populations. However, clinical PK data remain fragmented across study settings and are limited for special populations and individualized perioperative use, highlighting [...] Read more.

Background/Objectives: Cipepofol is a novel intravenous anesthetic whose pharmacokinetics (PK) may vary with dosing regimens, sampling sites, and physiological differences across populations. However, clinical PK data remain fragmented across study settings and are limited for special populations and individualized perioperative use, highlighting the need for a mechanistic modeling framework. This study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for cipepofol across diverse populations. Methods: Clinical data from nine studies were included, comprising 371 subjects and 3521 plasma concentration measurements. The model was established in healthy adults using HSK3486-101, qualified using healthy-adult data from HSK3486-111 and anesthesia induction datasets, and extrapolated to hepatic impairment, renal impairment, and elderly populations using pathophysiology-informed adjustments. Individualized external validation was further performed in adult and pediatric surgical patients using actual clinical dosing histories. Model performance was evaluated using concentration–time profiles, goodness-of-fit plots, fold error, and geometric mean fold error (GMFE) for C_max and AUC_0–t. Results: The model adequately described both arterial and venous plasma concentration–time profiles across the establishment, qualification, extrapolation, and external validation datasets. Most predicted concentrations were within two-fold of the observed values, and the overall GMFE values were 1.22 for C_max and 1.21 for AUC_0–t. Simulated exposure differences in hepatic impairment, renal impairment, and elderly subjects were generally limited, suggesting no clinically meaningful PK changes from a PK exposure perspective in these populations. The model also reproduced arterial–venous concentration differences and supported the major contributions of UGT1A9 and CYP2B6 to cipepofol clearance. Conclusions: This PBPK model provides a mechanistic framework for characterizing cipepofol disposition and may inform future model-informed dosing studies. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)

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28 pages, 5987 KB

Open AccessArticle

Textilinin-1, a Snake Venom-Derived Kunitz-Type Protease Inhibitor, Accelerates Wound Healing Through Anti-Inflammatory, Antibacterial, and Pro-Regenerative Activities

by Zhuo Chen, Huiwen Pang, Youzhi Wu, David M. Klyne, Xuqiang Nie, Pengfei Jiang, Xinfei Wu, Kong-Nan Zhao and Felicity Y. Han

Pharmaceutics 2026, 18(6), 762; https://doi.org/10.3390/pharmaceutics18060762 - 22 Jun 2026

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Abstract

Background/Objectives: Chronic wounds remain a formidable clinical challenge due to the suboptimal efficacy of conventional delivery systems and therapeutics. Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional [...] Read more.

Background/Objectives: Chronic wounds remain a formidable clinical challenge due to the suboptimal efficacy of conventional delivery systems and therapeutics. Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional biopharmaceutical for wound management remains largely untapped. This study evaluates the pharmacological effects of Textilinin-1 in preclinical models of cutaneous wound repair. Methods: We employed an integrated platform comprising bioinformatics, in vitro cellular assays, and in vivo murine excisional wounds and a pilot porcine proof-of-concept model to assess the wound healing-promoting effects of Textilinin-1 and explore associated cellular responses associated with key stages of the wound healing cascade. Results: Textilinin-1 was associated with multiple cellular responses relevant to tissue repair. It attenuated M1-like inflammatory activation and showed preliminary growth-inhibitory activity against Staphylococcus aureus under the tested conditions. Concurrently, it enhanced the proliferative and migratory capacity of fibroblasts, endothelial cells, and keratinocytes, which are key cellular targets for wound closure. In pre-clinical pilot porcine and rodent models, Textilinin-1 treatment was associated with accelerated wound contraction and improved structural tissue quality. Conclusions: Our findings provide preclinical evidence that Textilinin-1 may promote cutaneous wound repair and modulate cellular responses relevant to key stages of the wound healing cascade. These results support further investigation of Textilinin-1 as a candidate for wound repair applications. Future studies are required to define its precise molecular mechanisms, evaluate its efficacy in chronic or otherwise compromised wound models, and optimize its topical formulation or hydrogel-based delivery. Full article

(This article belongs to the Special Issue Drug Delivery and Therapeutic Strategies for Chronic Diseases and Pain)

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23 pages, 17391 KB

Open AccessArticle

Metformin and cRGDfc-Modified Nanoparticles Loaded with Curcumin for Age-Related Macular Degeneration: In Vitro Pharmacodynamics and Molecular Mechanisms

by Juan Liu, Ziheng Wang, Yuchang Yang, Lisha Yi, Shiman Li, Jingyi Gao, Jia Zhou, Nannan Cheng, Xingbin Yin, Xiaoxv Dong, Jian Ni and Changhai Qu

Pharmaceutics 2026, 18(6), 761; https://doi.org/10.3390/pharmaceutics18060761 - 22 Jun 2026

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Abstract

Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide [...] Read more.

Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of −23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway. Full article

(This article belongs to the Special Issue Ocular Drug Delivery Systems and Formulations)

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26 pages, 53555 KB

Open AccessArticle

Engineered Lipid Nanoparticles with Promoted Endosomal Escape and R283S-Mediated Stimulator of Interferon Genes (STING) Activation for Pancreatic Cancer Immunotherapy

by Sizhen Wang, Qiwei Tai, Kehui Wang, Jianyu Zheng, Beibei Guo, Feng Yang and Chen Wang

Pharmaceutics 2026, 18(6), 760; https://doi.org/10.3390/pharmaceutics18060760 - 21 Jun 2026

Viewed by 538

Abstract

Background/Objectives: Lipid nanoparticles (LNPs) have emerged as crucial vehicles for messenger RNA (mRNA) applications in antitumor therapy. Combining LNPs with stimulator of interferon genes (STING) activation holds promise for treating “cold” tumors such as pancreatic cancer. However, two major challenges remain: inefficient [...] Read more.

Background/Objectives: Lipid nanoparticles (LNPs) have emerged as crucial vehicles for messenger RNA (mRNA) applications in antitumor therapy. Combining LNPs with stimulator of interferon genes (STING) activation holds promise for treating “cold” tumors such as pancreatic cancer. However, two major challenges remain: inefficient mRNA escape from endosomes and STING pathway suppression in immunosuppressive tumor microenvironments. Methods: To improve endosomal escape, we developed a novel pH-responsive PEGylated lipid (Ben-mPEG₂₀₀₀) for mRNA-LNP preparation while using commercial Man-mPEG₂₀₀₀ for dendritic cell (DC)-targeted delivery of LNPs; to alleviate suppression of the STING pathway in the tumor microenvironment and activate immune responses, STING-R283S mRNA was encapsulated into LNPs, ultimately resulting in DC-targeted/pH-responsive LNPs loaded with STING-R283S mRNA for pancreatic cancer immunotherapy research. Results: After pH-responsive cleavage, Ben-mPEG₂₀₀₀ not only enhanced the positive charge of LNPs through the exposed protonated amino groups but also eliminated the PEG-induced steric hindrance effect. The combination of these two effects promoted membrane fusion between LNPs and the endosome, thereby enhancing mRNA translation. As a payload, STING-R283S could further amplify STING signaling in DCs without cytotoxicity to counteract immunosuppression in pancreatic cancer. Conclusions: This engineered LNP platform enhanced mRNA expression and STING activation in DCs, improving immunotherapy outcomes in pancreatic cancer. Full article

(This article belongs to the Section Nanomedicine and Nanotechnology)

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39 pages, 3065 KB

Open AccessReview

Mechanisms and Therapeutic Targets of Botanicals Derived from Asteraceae Plant Species

by Aphelele Taliwe, Siphamandla Q. N. Lamula, Lisa V. Buwa-Komoreng and Vuyolwethu Khwaza

Pharmaceutics 2026, 18(6), 759; https://doi.org/10.3390/pharmaceutics18060759 - 21 Jun 2026

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Abstract

The Asteraceae family represents one of the largest groups of medicinal plants, widely used in traditional medicine and increasingly investigated for its pharmacological potential. This review summarizes current evidence on the botanicals derived from Asteraceae plant species and their molecular mechanisms of action [...] Read more.

The Asteraceae family represents one of the largest groups of medicinal plants, widely used in traditional medicine and increasingly investigated for its pharmacological potential. This review summarizes current evidence on the botanicals derived from Asteraceae plant species and their molecular mechanisms of action against inflammation and cancer. Major classes of bioactive compounds in extracts are discussed in relation to their modulation of key signaling pathways and therapeutic targets such as NF-κB, MAPK, PI3K/Akt, COX-2, iNOS, and apoptotic regulators (Bax/Bcl-2, caspases). A literature search covering studies published between 2022 and 2026 was conducted. Evidence from in vitro, in vivo, and in silico studies demonstrates that Asteraceae-derived botanicals exert therapeutic effects through antioxidant activity, cytokine suppression, enzyme inhibition, and regulation of gene expression. Overall, the mechanistic insights presented herein support the rational use of Asteraceae medicinal plants and identify promising lead compounds for drug discovery and development. Full article

(This article belongs to the Special Issue Pharmaceutical Applications and Therapeutic Mechanisms of Substances from Plant Origin)

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30 pages, 7585 KB

Open AccessArticle

Investigation of the Photoprotective Effects of Various Pigments Against Laser-Marking of Pharmaceutical Tablets

by Hadi Shammout, Béla Hopp, Judit Kopniczky, Tamás Smausz, Bence Sipos, Katalin Kristó, János Bohus, Orsolya Jójárt-Laczkovich, Flórián Benkő, Tamás Sovány and Krisztina Ludasi

Pharmaceutics 2026, 18(6), 758; https://doi.org/10.3390/pharmaceutics18060758 - 21 Jun 2026

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Abstract

Background/Objectives: With the increasing incidence of drug counterfeiting and the emergence of personalized medicine, the need for unique marking of solid dosage forms, e.g., tablets, has attracted considerable interest in the current research and development landscape. Besides traditional printing methods, laser marking [...] Read more.

Background/Objectives: With the increasing incidence of drug counterfeiting and the emergence of personalized medicine, the need for unique marking of solid dosage forms, e.g., tablets, has attracted considerable interest in the current research and development landscape. Besides traditional printing methods, laser marking offers several advantages, as it eliminates the need for organic solvents and enables the generation of precise patterns. However, laser exposure may raise safety concerns regarding the stability of photosensitive drugs in the irradiated dosage forms. Therefore, the aim of the present study was to test the photoprotective effect of titanium dioxide (TiO₂) and its various alternatives, e.g., talc, calcium carbonate (CaCO₃), zinc oxide (ZnO), and black iron oxide (Fe₃O₄), alongside a ready-to-use reference formulation, Opadry^® Brown, which contains TiO₂ (titanium-containing, TC) on nifedipine, a light-sensitive model drug. Methods: Laser marking or short-term laser ablation at different wavelengths (193 nm, 248 nm, 532 nm, and 781 nm) was applied to different coating formulations. As a positive control, prolonged exposure to daylight was applied. The properties and photostability of these formulations were evaluated using several analytical methods (i.e., surface profilometry, Raman spectroscopy, and high-performance liquid chromatography (HPLC)). Results: The TiO₂, ZnO, Fe₃O₄, and Opadry^® TC Brown coatings maintained their color during the long-term study under all conditions. Furthermore, the prepared formulations exhibited different ablation depths and morphological changes depending on the coating and laser type. HPLC measurements confirmed significant differences in the protective ability of various pigments against sunlight and different types of lasers. Nevertheless, the obtained Raman spectra were not in complete agreement with HPLC results, which can be attributed to spectral overlap between key nifedipine degradation markers and excipient signals in the tablet core. Conclusions: Overall, laser treatment of tablets containing photosensitive drugs may induce API decomposition; however, this effect can be minimized or avoided by careful selection of the appropriate combination of laser type and photoprotective pigment. Under the applied experimental conditions, Ti:Sa laser treatment was associated with the lowest degree of nifedipine degradation among all formulations, while ZnO-containing coatings demonstrated the most consistent photoprotective performance against the majority of the tested laser types, while Fe₃O₄-containing coatings provided superior protection during prolonged sunlight exposure and Nd:YAG laser irradiation. Full article

(This article belongs to the Special Issue Dosage Forms in Drug Delivery: State of the Art and Future Perspectives, 2nd Edition)

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22 pages, 2946 KB

Open AccessArticle

A Systemically Administered Humanized Anti-Nav1.7 Antibody with Long-Lasting Analgesic Activity and Preserved Physiological Nociception

by Sosuke Yoneda, Daisuke Uta, Kana Yasufuku, Takuya Yamane, Saho Yoshioka, Keiko Takasu, Takaya Izumi, Sayaka Fujita, Daiki Nakamori, Shiori Kawasaki, Tatsuya Takahashi, Mai Yoshikawa, Koichi Ogawa and Erika Kasai

Pharmaceutics 2026, 18(6), 757; https://doi.org/10.3390/pharmaceutics18060757 - 21 Jun 2026

Viewed by 505

Abstract

Background: Neuropathic pain remains difficult to treat because current analgesics often provide insufficient efficacy or dose-limiting adverse effects. Nav1.7 is genetically validated as a key regulator of human pain sensation, but the development of selective small-molecule Nav1.7 inhibitors has been limited by the [...] Read more.

Background: Neuropathic pain remains difficult to treat because current analgesics often provide insufficient efficacy or dose-limiting adverse effects. Nav1.7 is genetically validated as a key regulator of human pain sensation, but the development of selective small-molecule Nav1.7 inhibitors has been limited by the high similarity among voltage-gated sodium channel subtypes. Methods: We generated monoclonal antibodies selectively targeting Nav1.7, humanized them for therapeutic development, and evaluated their binding, selectivity, functional channel inhibition, systemic analgesic efficacy, and effects on neuronal activity in a rat model of partial sciatic nerve ligation-induced neuropathic pain. Results: The humanized antibodies showed high-affinity and selective binding to Nav1.7 and functionally inhibited the channel in cellular assays. After systemic administration to neuropathic pain model rats, the lead antibody produced robust analgesia lasting at least 96 h. Electrophysiological analyses demonstrated reduced mechanically evoked and spontaneous neuronal activity, and immunohistochemistry showed decreased mechanical stimulus-induced phosphorylation of extracellular signal-regulated kinase in dorsal root ganglion neurons. The antibodies did not impair physiological nociception or motor function under the tested conditions. Conclusions: These findings provide preclinical proof of concept that humanized anti-Nav1.7 antibodies can act as systemically administered, long-acting biologic analgesics for neuropathic pain while preserving normal nociceptive and motor functions. The clinical advancement of S-151128 further supports the translational potential of this modality. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)

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14 pages, 1345 KB

Open AccessArticle

A Functional Data Analysis-Based Framework for Modeling and Multi-Objective Optimization of Sustained-Release Drug Delivery Systems

by Hao Ren, Mengchen Han, Yuchao Qiao, Yu Cui, Chongqi Hao, Yiming Lou, Gaomin Jing, Qiankun Liu, Lang Yang, Li Zheng and Lixia Qiu

Pharmaceutics 2026, 18(6), 756; https://doi.org/10.3390/pharmaceutics18060756 - 21 Jun 2026

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Abstract

Objectives: An integrated methodological framework was developed for modeling and multiobjective optimization of sustained-release drug delivery systems. Methods: The cumulative release percentage was fitted as a function curve, and functional principal component analysis was subsequently used to transform the function curves [...] Read more.

Objectives: An integrated methodological framework was developed for modeling and multiobjective optimization of sustained-release drug delivery systems. Methods: The cumulative release percentage was fitted as a function curve, and functional principal component analysis was subsequently used to transform the function curves into functional principal component scores (FPCs). FPCs were then treated as dependent variables, while the proportions of the formulation factors were used as independent variables to construct Scheffé polynomial regression models. Finally, Non-dominated Sorting Genetic Algorithm III (NSGA-III) was applied to perform multi-objective optimization. Results: FPC1, FPC2, and FPC3 captured 95.18%, 4.39%, and 0.32% of the total variation, respectively. Corresponding Scheffé polynomial regression models were established, including quadratic models for FPC1 (adjusted R² = 0.751, AIC = 168.557) and FPC2 (adjusted R² = 0.592, AIC = 119.302), and a special cubic model for FPC3 (adjusted R² = 0.597, AIC = 64.574). The NSGA-III algorithm generated a Pareto optimal set, yielding stable formulation compositions with mean (SD) values of X₁ = 0.123 (0.015), X₂ = 0.821 (0.032), X₃ = 0.012 (0.017), and X₄ = 0.045 (0.015). The corresponding FPCs were −41.787 (2.544), 10.009 (0.168), and 8.264 (0.010) for FPCs1–FPCs3, respectively. The reconstructed cumulative release percentages were 42.471 (1.661), 52.623 (2.868), 69.942 (1.200), 84.275 (1.010), and 93.330 (0.832), demonstrating good agreement with the target release profiles. Conclusions: The integrated FDA–Scheffé–NSGA-III framework provides a robust and effective approach for accurately modeling release behavior and optimizing sustained-release formulations. Full article

(This article belongs to the Section Physical Pharmacy and Formulation)

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40 pages, 1741 KB

Open AccessReview

An Overview of Advanced Materials and Manufacturing Strategies for 3D-Printed Bioengineered Vascular Stents: Toward Next-Generation Drug Delivery Applications

by Faisal Khaled Aldawood

Pharmaceutics 2026, 18(6), 755; https://doi.org/10.3390/pharmaceutics18060755 - 21 Jun 2026

Viewed by 345

Abstract

Additive manufacturing has emerged as a transformative technology for fabricating complex drug-eluting medical devices, offering unprecedented design freedom and functional integration capabilities. This comprehensive review systematically analyzes 3D printing technologies applied to pharmaceutical device manufacturing, focusing on drug-eluting vascular stents as a representative [...] Read more.

Additive manufacturing has emerged as a transformative technology for fabricating complex drug-eluting medical devices, offering unprecedented design freedom and functional integration capabilities. This comprehensive review systematically analyzes 3D printing technologies applied to pharmaceutical device manufacturing, focusing on drug-eluting vascular stents as a representative application. This review covers six primary additive manufacturing techniques, ranging from high-resolution vat photopolymerization (25 μm resolution) to direct energy deposition, with a focus on their capabilities for produce pharmaceutical devices with controlled drug release properties. Novel 4D/5D/6D printing technologies introduce stimuli-responsive behaviors enabling programmable drug release profiles and adaptive device functionality. Manufacturing process optimization reveals superior design flexibility compared to conventional methods, with 85–95% reduction in design iteration time and elimination of tooling costs for complex geometries. The material landscape encompasses traditional metals (316L stainless steel, cobalt–chromium), biodegradable polymers (polylactic acid, PLA; polycaprolactone, PCL; poly(lactic-co-glycolic acid), PLGA), shape-memory materials (i.e., polymers and alloys capable of recovering a pre-programmed shape upon exposure to a specific stimulus such as body temperature, moisture, or light), and advanced nanocomposites, each offering distinct drug-loading capacities (100–500 μg/cm²) and release kinetics. Critical challenges include standardization requirements (International Organization for Standardization (ISO) 5840 and American Society for Testing and Materials (ASTM) F2606), pharmaceutical-grade manufacturing protocols, and regulatory pathways for novel drug-device combinations. This review identifies key research priorities including development of biocompatible printing materials, accelerated drug release testing protocols, and scalable manufacturing processes suitable for medical device production. This analysis demonstrates that 3D printing enables integration of multiple pharmaceutical functions within single devices, controlled spatiotemporal drug delivery, and elimination of secondary manufacturing steps for drug coating processes, advancing the development of next-generation therapeutic medical devices. Full article

(This article belongs to the Special Issue Biomedical Applications: Advances in Bioengineering and Drug Delivery, 2nd Edition)

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26 pages, 19471 KB

Open AccessArticle

Benzofuran-Annulated Naphthalimides Trigger Replication Stress, DNA Damage, and p53-Dependent Cell Cycle Arrest

by Zlatina Vlahova, Lazar Lazarov, Maria Petrova, Shazie Yusein-Myashkova, Jordana Todorova, Maria Schröder, Monika Mutovska, Stanimir Stoyanov, Yulian Zagranyarski and Iva Ugrinova

Pharmaceutics 2026, 18(6), 754; https://doi.org/10.3390/pharmaceutics18060754 - 20 Jun 2026

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Abstract

Background/Objectives: DNA-targeting small molecules that induce replication stress represent a promising strategy in anticancer drug development. 1,8-Naphthalimide (NI) derivatives are well-established DNA-intercalating agents, and heterocyclic annulation offers a rational approach to enhancing their potency and tumor selectivity. Here, we report the synthesis and [...] Read more.

Background/Objectives: DNA-targeting small molecules that induce replication stress represent a promising strategy in anticancer drug development. 1,8-Naphthalimide (NI) derivatives are well-established DNA-intercalating agents, and heterocyclic annulation offers a rational approach to enhancing their potency and tumor selectivity. Here, we report the synthesis and biological evaluation of a novel series of benzofuran-containing naphthalimide derivatives, with particular focus on the lead dinitro-substituted compound 5d. Methods: Cytotoxic activity was assessed using the MTT assay in A549 (p53 wild-type), H1299 (p53-null), and MRC-5 cells. Long-term antiproliferative effects were evaluated by clonogenic survival assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Replication stress and DNA damage were quantified by EdU incorporation and γH2AX immunofluorescence, respectively. Apoptosis was assessed by Annexin V/PI staining and caspase-3/7 activation assay. p53 nuclear accumulation and autophagy induction were evaluated by immunofluorescence and Western blot, using LC3 as an autophagic marker. Results: All compounds exhibited cytotoxic activity in the nanomolar range, with 5d emerging as the most potent and selective. Clonogenic survival was significantly reduced, indicating durable suppression of proliferative capacity. Treatment with 5d induced G₁ arrest in A549 cells and the accumulation of H1299 cells in G₂/M, consistent with p53-dependent and p53-independent checkpoint activation, respectively. EdU incorporation was markedly reduced, while γH2AX intensity increased, collectively supporting a replication stress-driven mechanism of DNA damage. Apoptosis was confirmed by increased Annexin V-positive populations and caspase-3/7 activation. LC3 puncta formation and LC3-I/LC3-II conversion were increased, indicating LC3 processing and autophagosome accumulation consistent with the activation of autophagy-related processes. Conclusions: 5d induces a cellular phenotype consistent with replication stress, including reduced EdU incorporation, γH2AX accumulation, cell cycle arrest, and apoptotic cell death in a p53 status-dependent manner. These findings establish benzofuran-annulated naphthalimides as a promising scaffold for the development of anticancer agents that exploit replication stress vulnerabilities in tumor cells. Full article

(This article belongs to the Section Drug Targeting and Design)

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25 pages, 1032 KB

Open AccessArticle

Mucoadhesive Nanostructured Lipid Carriers of Ketoconazole for Enhanced Dermal Delivery and Antifungal Activity: Formulation Optimization and In Vivo Evaluation

by Mashan Almutairi, Ahmed Adel Ali Youssef, Yazed S. Alsowaida, Ahmed Alobaida and Samir A. Ross

Pharmaceutics 2026, 18(6), 753; https://doi.org/10.3390/pharmaceutics18060753 - 19 Jun 2026

Viewed by 485

Abstract

Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical [...] Read more.

Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol^® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article

(This article belongs to the Special Issue Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery)

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26 pages, 2547 KB

Open AccessReview

Genetic Interruption of PD-1/PD-L1 as an Alternative Means for Immune Checkpoint Blockade in Cancer: A Review

by Dan Li, Jiao Lu, Qianru Li, Huan Deng and Songwei Tan

Pharmaceutics 2026, 18(6), 752; https://doi.org/10.3390/pharmaceutics18060752 - 18 Jun 2026

Viewed by 477

Abstract

Background/Objectives: Immune checkpoints are critical regulatory pathways that maintain peripheral tolerance and prevent autoimmunity. Among these, the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis serves as a major inhibitory pathway that terminates T cell responses. While protein-based checkpoint blockade (ICB) targeting this axis [...] Read more.

Background/Objectives: Immune checkpoints are critical regulatory pathways that maintain peripheral tolerance and prevent autoimmunity. Among these, the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis serves as a major inhibitory pathway that terminates T cell responses. While protein-based checkpoint blockade (ICB) targeting this axis has revolutionized clinical cancer therapy, its clinical efficacy is frequently limited by low response rates, immune-related adverse events (irAEs), and the emergence of adaptive resistance. To break through these bottlenecks, genetic interruption has emerged as a high-precision alternative to modulate the PD-1/PD-L1 pathway at the nucleotide level. Methods: A comprehensive systematic review of literature was performed across major databases (PubMed, Web of Science), with a focus on high quality studies published up to 2026. Results: Direct genomic disruption via CRISPR/Cas9 and post-transcriptional silencing through RNA interference can effectively neutralize inhibitory signaling at its source. Recent advances demonstrate that targeting upstream regulatory nodes—including metabolic checkpoints (e.g., lactate metabolism) and biophysical mechanisms (e.g., liquid–liquid phase separation)—provides superior transcriptional control over PD-L1. Furthermore, engineering CAR-T cells with multiplex gene editing (e.g., TCR/B2M/PD-1 knockout) or localized scFv secretion significantly enhances antitumor potency while reducing systemic toxicity. Innovations in organ-targeted lipid nanoparticles and stimuli-responsive biomimetic carriers further address the delivery barriers in solid tumors. Conclusions: Gene therapy provides a high-precision platform for PD-1/PD-L1 modulation, offering a viable strategy to overcome adaptive resistance. Future clinical application depends on the refinement of safer editing tools, such as base editing, and the standardization of intelligent delivery systems to ensure controllable and scalable cancer immunotherapy. Full article

(This article belongs to the Section Gene and Cell Therapy)

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22 pages, 2339 KB

Open AccessArticle

A Novel Herbal Nano-Based Ear Drop with Ocimum gratissimum Essential Oil: An Alternative Strategy for Managing Otomycosis

by Bac V. G. Nguyen, Hoai Thu Le, Tien-Trung Dao, Quy-Nguyen Doan, Duc-Huy Pham, Nghi Bao Nguyen, Minh-Tri Le, Du-Thien Nguyen and Phuoc-Vinh Nguyen

Pharmaceutics 2026, 18(6), 751; https://doi.org/10.3390/pharmaceutics18060751 - 18 Jun 2026

Viewed by 416

Abstract

Background/Objectives: Otomycosis is a recurrent fungal infection of the external auditory canal. This disease is difficult to manage with current antifungal agents due to irritation, ototoxicity risk, and emerging resistance. Natural essential oils have been proposed as alternatives, yet their clinical application [...] Read more.

Background/Objectives: Otomycosis is a recurrent fungal infection of the external auditory canal. This disease is difficult to manage with current antifungal agents due to irritation, ototoxicity risk, and emerging resistance. Natural essential oils have been proposed as alternatives, yet their clinical application in otic formulations remains limited due to their poor solubility and stability. In this study, we report the first ear-drop formulation combining microemulsified Ocimum gratissimum essential oil and acetic acid for otomycosis treatment. Methods: The essential oil was quality-validated with eugenol content superior to 60%. A systematic formulation study was performed, and the Tween 20/isopropanol (4:1, w/w) mixture was selected as the optimal surfactant system, yielding a stable microemulsion with high encapsulation efficiency (~98%) and relevant physicochemical stability (up to 28 days). The final formulation containing 1% acetic acid and 0.3% micro-emulsified essential oil met pharmacopeial requirements in terms of appearance, pH, viscosity, and microbial limits. Results: Importantly, this micro-emulsified eardrop demonstrated significantly greater in vitro antifungal activity than 3% boric acid and 2% acetic acid eardrops in twelve clinical fungal isolates from Vietnamese swimmers, especially on Curvularia, Cunninghamella, Aspergillus terreus, and Bipolaris. Although less pronounced than 1% clotrimazole, the finalized formulation demonstrates better antifungal kinetics and a broader activity spectrum. Conclusions: This work provides relevant experimental evidence on the use of Ocimum gratissimum essential oil in a microemulsion delivery system and demonstrates its efficacy against clinically relevant otomycosis pathogens. The results establish a foundation for future in vivo and clinical studies. Full article

(This article belongs to the Special Issue Nanoemulsions for Pharmaceutical and Biomedical Applications)

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32 pages, 23726 KB

Open AccessReview

Medicinal Plant-Derived Exosome-like Nanoparticles: From Basic Research to Biomedical Applications

by Huan Deng, Yi-Wen Zhang, Qian-Fu Zhao and Zhi-Jun Huang

Pharmaceutics 2026, 18(6), 750; https://doi.org/10.3390/pharmaceutics18060750 (registering DOI) - 18 Jun 2026

Viewed by 380

Abstract

Plant-derived exosome-like nanoparticles (PELNs), a subset of extracellular vesicle (EV) secreted by plant cells, have emerged as revolutionary biomaterial with broad applications in biomedicine, agriculture, and nanotechnology. Structurally, PELNs feature a phospholipid bilayer homologous to plant cell membranes, encapsulating bioactive components such as [...] Read more.

Plant-derived exosome-like nanoparticles (PELNs), a subset of extracellular vesicle (EV) secreted by plant cells, have emerged as revolutionary biomaterial with broad applications in biomedicine, agriculture, and nanotechnology. Structurally, PELNs feature a phospholipid bilayer homologous to plant cell membranes, encapsulating bioactive components such as proteins, nucleic acids, lipids, and secondary metabolites. The native structure of PELNs endows them with enhanced bioavailability, reduced immunogenicity, and improved barrier penetration for precise tissue delivery. Recent studies highlight the cross-kingdom therapeutic potential of PELNs in mammals, including antitumor, anti-inflammatory, tissue repair, immunomodulation and so on. This review comprehensively summarized recent advancements in PELN research, including innovative isolation techniques, molecular characterization, their roles in drug delivery and disease therapy. We also discussed challenges in standardization, scalability, and regulatory frameworks which could provide future perspectives for translating PELNs into clinical and industrial applications. Full article

(This article belongs to the Special Issue Delivery System for Biomacromolecule Drugs: Design and Application, 2nd Edition)

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19 pages, 6304 KB

Open AccessArticle

Preformulation Studies and Rational Design of an Ointment Containing a Postbiotic Metabolite of Procyanidins for Topical Use

by Tomasz Todryk, Monika Budnicka, Lukasz Pajchel, Hanna Kierońska, Maciej Dawidowski, Krzysztof Adam Stępień, Joanna Giebułtowicz, Sebastian Granica, Joanna Kolmas and Jakub P. Piwowarski

Pharmaceutics 2026, 18(6), 749; https://doi.org/10.3390/pharmaceutics18060749 - 18 Jun 2026

Viewed by 483

Abstract

Background: 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a postbiotic gut microbiota-derived flavanol metabolite with reported anti-inflammatory activity. Despite growing interest in its potential dermatological applications, its pharmaceutical properties and suitability for topical delivery have not been systematically investigated. This study aimed to perform the first comprehensive [...] Read more.

Background: 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a postbiotic gut microbiota-derived flavanol metabolite with reported anti-inflammatory activity. Despite growing interest in its potential dermatological applications, its pharmaceutical properties and suitability for topical delivery have not been systematically investigated. This study aimed to perform the first comprehensive preformulation and formulation-oriented evaluation of DHPV and to develop stable topical ointment formulations suitable for further dermatological research. Methods: The physicochemical properties of DHPV were characterized using powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), quantitative solubility assessment, and excipient compatibility studies. Based on the obtained preformulation data, two anhydrous ointment formulations containing DHPV were developed. The formulations were evaluated for homogeneity, rheological behavior, chemical stability under accelerated storage conditions, and in vitro drug release performance. Results: DHPV was identified as a crystalline compound with heterogeneous particle morphology and limited aqueous solubility. Quantitative solubility studies demonstrated the highest solubility in PEG 300 and glycol-based solvents. Compatibility testing revealed increased impurity formation in hydrophilic environments, whereas lipophilic excipients provided improved chemical stability. Both ointment formulations exhibited acceptable physical characteristics and maintained DHPV stability throughout accelerated storage. However, marked differences in release behavior were observed. The lipid–wax formulation showed significantly higher release rates, lower variability, and more reproducible release profiles than the petrolatum-based reference formulation, indicating more efficient diffusion of DHPV from the semisolid matrix. Conclusions: The physicochemical characteristics of DHPV strongly influence formulation design and performance. Anhydrous lipid-based systems provide a favorable environment for maintaining DHPV stability, while formulation composition significantly affects drug release. The developed lipid–wax formulation represents a promising platform for future skin permeation, pharmacodynamic, and efficacy studies. Full article

(This article belongs to the Special Issue Research on the Design, Development and Delivery of Topical Drugs)

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20 pages, 1262 KB

Open AccessArticle

Formulation and Evaluation of Fluconazole Containing Sodium Alginate/Methylcellulose-Based Buccal Films for Potential Treatment of Oral Candidiasis

by Adekunle Oduneye Odularu, Anuoluwapo Temitope Adesegun, Chukwuemeka Paul Azubuike and Oluwadamilola Miriam Kolawole

Pharmaceutics 2026, 18(6), 748; https://doi.org/10.3390/pharmaceutics18060748 - 18 Jun 2026

Viewed by 492

Abstract

Background/Objectives: Oral candidiasis is an infection of the oral cavity caused by Candida albicans. Mucoadhesive buccal films could adhere to the buccal mucosa for prolonged periods, improving the therapeutic outcomes of patients with oral candidiasis. This study aimed to develop and [...] Read more.

Background/Objectives: Oral candidiasis is an infection of the oral cavity caused by Candida albicans. Mucoadhesive buccal films could adhere to the buccal mucosa for prolonged periods, improving the therapeutic outcomes of patients with oral candidiasis. This study aimed to develop and evaluate the properties of fluconazole containing sodium alginate/methylcellulose-based buccal films for potential treatment of oral candidiasis. Methods: Drug-polymer compatibility was investigated using FT-IR spectrophotometry. Three optimised fluconazole films (F1 to F3) containing 1–1.6% sodium alginate and methylcellulose (1.6%) were formulated using the solvent-casting method. Their physicomechanical properties were characterised using standard protocols. Drug content and in vitro drug release profiles were evaluated using UV-visible spectroscopy; in vitro/ex vivo mucoadhesion studies were conducted using the shaking water bath technique, and their antifungal activity against Candida albicans was evaluated using the agar ditch method. Results: FT-IR data analysis revealed that sodium alginate, methylcellulose and fluconazole were compatible in the films. The films were off-white, smooth, peelable, thin, with satisfactory pH values, folding endurance, drug content, excellent zones of inhibition against Candida albicans (40 mm), controlled drug release profile (3.6–4.1 mg/cm² after 6 h), and they displayed Korsmeyer–Peppas drug release kinetics. Film F3 containing 1.6% sodium alginate and 1.6% of methylcellulose exhibited superior swelling index (70 ± 1%), tensile strength (0.68 ± 0.04 MPa) and in vitro/ex vivo mucoadhesion time (5.5 ± 0.3 h; 2.3 ± 0.3 h) relative to other studied films. Conclusions: The sodium alginate content of the films influenced their tensile and mucoadhesive properties. Film F3 was the most promising formulation for potential treatment of oral candidiasis. Full article

(This article belongs to the Section Biopharmaceutics)

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30 pages, 27534 KB

Open AccessArticle

Supercritical CO₂ Antisolvent-Micronised Naringin and Naringenin Alleviate Paclitaxel-Induced Pain Syndrome

by Gabriela Adriany Lisboa Zilli, Samara Cristina Mazon, Patricia Viera de Oliveira, Felipe Zaniol, Eulália Lopes da Silva Barros, Ângela Maria Lodi, Chaiane Lunelli Saretto, Hemyly Cardoso, Ana Lúcia Anversa Segatto, Sara Marchesan Oliveira, J. Vladimir Oliveira and Indiara Brusco

Pharmaceutics 2026, 18(6), 747; https://doi.org/10.3390/pharmaceutics18060747 - 17 Jun 2026

Viewed by 547

Abstract

Background/Objectives: Paclitaxel is a chemotherapy drug used to treat various tumours, but its use is often limited by an acute and chronic pain syndrome that is poorly managed. Naringin and its aglycone, naringenin, exhibit antioxidant, antitumour, anti-inflammatory, and antinociceptive effects, [...] Read more.

Background/Objectives: Paclitaxel is a chemotherapy drug used to treat various tumours, but its use is often limited by an acute and chronic pain syndrome that is poorly managed. Naringin and its aglycone, naringenin, exhibit antioxidant, antitumour, anti-inflammatory, and antinociceptive effects, making them potential alternative treatments. However, their low water solubility limits their oral bioavailability in humans. Micronisation in a supercritical medium reduces particle size and enhances the dissolution of compounds, offering a possible solution. In this study, we investigated whether micronising naringin and naringenin via supercritical technology could improve their dissolution and oral efficacy against paclitaxel-induced pain syndrome. Methods: Micronisation was performed using supercritical CO₂. Molecular docking was used to analyse the binding of naringin and naringenin to TRPV1, a key target for pain relief. Swiss mice were used in capsaicin (TRPV1 agonist)-induced nociception and paclitaxel-caused acute and chronic pain models. We assessed mechanical, cold, and heat sensitivity, potential adverse effects, and TRPV1 mRNA expression. Results: Micronisation improved the apparent dissolution profile of molecules. Docking results showed that naringin and naringenin bind to TRPV1. Both micronised compounds reduced capsaicin-induced nociception without affecting locomotion or body temperature. Micronised naringin and naringenin alleviated mechanical and cold allodynia, as well as thermal hyperalgesia in both acute and chronic paclitaxel-induced pain, outperforming their conventional forms. They also downregulated TRPV1 mRNA expression in the mice’s sciatic nerve. Conclusions: Taken together, these results show that supercritical micronisation improved the apparent dissolution and oral antinociceptive efficacy of naringin and naringenin, emphasising their potential as promising alternatives for managing paclitaxel-induced pain, with TRPV1 being a probable contributor to the observed antinociceptive effects. Full article

(This article belongs to the Special Issue Advances in Polymer-Based Devices and Platforms for Pain Management)

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19 pages, 2977 KB

Open AccessArticle

Thymoquinone-Loaded Electrospun Fibrous Mats as Advanced Wound Dressing Materials

by Magdalena Paczkowska-Walendowska, Elwira Sieniawska, Zbigniew Krasiński, Judyta Cielecka-Piontek and Krystyna Skalicka-Woźniak

Pharmaceutics 2026, 18(6), 746; https://doi.org/10.3390/pharmaceutics18060746 - 17 Jun 2026

Viewed by 450

Abstract

Background: Thymoquinone (TQ), a bioactive compound derived from Nigella sativa L., exhibits promising antioxidant, anti-inflammatory, and wound-healing properties; however, its clinical application is limited by poor solubility and instability. Methods: In this study, three electrospun nanofiber systems based on different polymeric matrices, PVP [...] Read more.

Background: Thymoquinone (TQ), a bioactive compound derived from Nigella sativa L., exhibits promising antioxidant, anti-inflammatory, and wound-healing properties; however, its clinical application is limited by poor solubility and instability. Methods: In this study, three electrospun nanofiber systems based on different polymeric matrices, PVP (N1), PVP/HPβCD (N2), and PVP/PCL (N3), were developed as potential wound dressing materials for controlled TQ delivery. Results: All formulations produced uniform nanofibrous structures with TQ molecularly dispersed within the polymer matrix, as confirmed by SEM, XRPD, and FTIR analyses. The composition of the nanofibers significantly influenced their physicochemical and functional properties. The N2 system, containing hydroxypropyl-β-cyclodextrin (HPβCD), exhibited the smallest fiber diameter (~208 nm), the fastest drug release, and enhanced antioxidant and anti-inflammatory activity due to improved TQ solubility. In contrast, the N3 system, incorporating polycaprolactone (PCL), formed thicker fibers (~1089 nm) and demonstrated sustained release behavior, the highest mucoadhesion, and the most pronounced wound-healing effect (90% closure after 24 h). Stability studies revealed that HPβCD significantly improved TQ resistance to thermal, humidity, and photolytic degradation, whereas the PVP-based system without stabilizers showed the lowest stability. Principal component analysis (PCA) confirmed that nanofiber performance is governed by two key factors: drug availability and sustained release combined with bioadhesion. Importantly, wound-healing efficiency correlated more strongly with the latter. Conclusions: The results demonstrate that rational design of polymer composition enables modulation of TQ delivery and biological response. Among the tested systems, PVP/PCL nanofibers appear to be the most promising candidates for wound-dressing applications due to their ability to provide sustained drug release and enhance tissue regeneration. Full article

(This article belongs to the Section Nanomedicine and Nanotechnology)

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26 pages, 19353 KB

Open AccessArticle

Development and Characterization of a Stable Oil-in-Water Nanoemulsion Using Impingement Jet Mixing and Lyophilization Techniques

by Anna Shao, Jingyan Zhang, Zhaowei Jin, Yao Li, Jialin Tang, Quanmin Chen, Hongbing Wu and Jeremy Guo

Pharmaceutics 2026, 18(6), 745; https://doi.org/10.3390/pharmaceutics18060745 - 17 Jun 2026

Viewed by 443

Abstract

Nanoemulsion (NEM) is an effective adjuvant and delivery system for vaccines and nucleic acids, capable of inducing immune responses against diverse pathogens. Background/Objectives: Conventional NEM manufacture uses multi-step operations, typically high-shear homogenization and then microfluidization (HSHM), thereby increasing process complexity and contamination [...] Read more.

Nanoemulsion (NEM) is an effective adjuvant and delivery system for vaccines and nucleic acids, capable of inducing immune responses against diverse pathogens. Background/Objectives: Conventional NEM manufacture uses multi-step operations, typically high-shear homogenization and then microfluidization (HSHM), thereby increasing process complexity and contamination risk. As water-rich colloidal dispersions, NEM is prone to microbial proliferation and droplet coalescence; freezing further disrupts microstructure, causing phase fusion and separation, so NEM adjuvants are often stored separately from antigens in multi-vial formats. Lyophilization could reduce cold-chain dependence and enable single-vial products, but there is no systematic study on lyoprotectants comparation and process optimization of lyophilized NEM. Methods: An impingement jet mixing (IJM) process was evaluated as a simplified, scalable route for NEM production. Key IJM parameters, including flow ratio, total flow rate, preparation temperature, microchannel type, and shear mode—were examined to match attributes of conventional HSHM. Lyophilized and reconstituted NEM were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and/or in vitro potency to inform lyoprotectant selection, and Taguchi Design of Experiment (DOE) methodology guided lyophilization processes. Results: IJM yielded NEM with droplet size, polydispersity index (PDI) and morphology comparable to HSHM, with higher throughput and fewer unit operations. Optimized lyophilization technique with designed lyoprotectant and process formed closed structures to prevent the easy-to-flow monolayer of the emulsion from fusing, producing robust and stable NEM. Conclusions: Coupling IJM with targeted lyophilization establishes a scalable, lower-risk manufacturing paradigm for NEM that preserves critical quality attributes, reduces cold-chain reliance and enables single-vial adjuvanted vaccine formats with tangible industrial and clinical benefits. Full article

(This article belongs to the Special Issue Advancements in Industrial Pharmaceutics: Innovations and Future Directions)

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30 pages, 4393 KB

Open AccessReview

Polymeric Micelle Systems for Oral Drug Delivery of Small Molecule Therapeutics

by Eungyeop Lee, Jun Bum Kwon, Hyuk Jun Cho, Mi Ran Woo, Dong Wuk Kim, Jong Oh Kim and Duhyeong Hwang

Pharmaceutics 2026, 18(6), 744; https://doi.org/10.3390/pharmaceutics18060744 - 16 Jun 2026

Viewed by 437

Abstract

Oral administration remains the most convenient and favored route for systemic delivery of small-molecule drugs, primarily due to patient compliance and the absence of invasive procedures. Yet, poor aqueous solubility, chemical/enzymatic instability, and limited permeability in the gastrointestinal (GI) tract often result in [...] Read more.

Oral administration remains the most convenient and favored route for systemic delivery of small-molecule drugs, primarily due to patient compliance and the absence of invasive procedures. Yet, poor aqueous solubility, chemical/enzymatic instability, and limited permeability in the gastrointestinal (GI) tract often result in low bioavailability (BA) of many therapeutic agents. Polymeric micelles formed from the self-assembly of amphiphilic block copolymers have gained considerable attention as a nanotechnology-driven solution to overcome these challenges. Their hydrophobic core–hydrophilic shell structure enables efficient encapsulation of poorly soluble small molecule drugs, providing protection from acidic or enzymatic degradation while potentially enhancing drug transport across the intestinal epithelium. This review examines the design principles, formulation strategies, and in vivo performance of polymeric micelles for oral delivery of small molecule drugs. We discuss strategies to improve micelle stability in the GI environment, including optimization of core hydrophobicity, kinetic stabilization, and corona engineering, and compare polymeric micelles with established alternatives such as self-micro emulsifying drug delivery system (SMEDDS) and amorphous solid dispersions (ASDs) across critical performance parameters. Despite decades of preclinical progress, no oral polymeric micelle formulation has reached regulatory approval, underscoring the persistent challenge of maintaining micellar structural integrity under the dynamic conditions of the GI environment. This review therefore examines not only the promise but also the structural vulnerabilities of oral micelles, proposing a stability-centered framework for interpreting micelle function under GI conditions. Finally, we discuss current translational challenges and suggest directions for future research toward clinical application of oral polymeric micelle systems. Full article

(This article belongs to the Special Issue Polymer Systems for Drug-Delivery Applications)

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24 pages, 4958 KB

Open AccessReview

Interpreting the Black Box: Interpretable Machine Learning and Systems Pharmacology in Small-Molecule Therapeutics

by Huan Zhang, Yangyang Wang, Jihan Wang and Hui Li

Pharmaceutics 2026, 18(6), 743; https://doi.org/10.3390/pharmaceutics18060743 (registering DOI) - 16 Jun 2026

Viewed by 473

Abstract

Small-molecule drug development faces high attrition rates driven by complex pharmacokinetics and unforeseen toxicities. While deep learning offers high predictive accuracy, its opaque “black-box” nature hinders mechanistic transparency, clinical trust, and regulatory approval. This review synthesizes how Interpretable Machine Learning, synergized with systems [...] Read more.

Small-molecule drug development faces high attrition rates driven by complex pharmacokinetics and unforeseen toxicities. While deep learning offers high predictive accuracy, its opaque “black-box” nature hinders mechanistic transparency, clinical trust, and regulatory approval. This review synthesizes how Interpretable Machine Learning, synergized with systems pharmacology, advances this paradigm by enhancing mechanistic transparency in drug development. By providing insights into algorithmic decisions, Interpretable Machine Learning helps researchers identify molecular features that are statistically associated with absorption, distribution, metabolism, and excretion optimization and preemptively mitigate toxicophores, while noting that these associations require experimental validation to establish genuine causality. Furthermore, integrating multi-omics data via Interpretable Machine Learning guides rational polypharmacology, bridging in silico target identification with “dry-wet loop” validations. Crucially, Interpretable Machine Learning accelerates clinical translation by discovering causal biomarkers, refining patient stratification, and generating transparent “Model Cards” to satisfy U.S. Food and Drug Administration/European Medicines Agency regulations. We also discuss future challenges: data heterogeneity, out-of-distribution generalizability, and the evolution toward Causal Artificial Intelligence. Ultimately, the integration of Interpretable Machine Learning provides a framework for more transparent and evidence-based drug design, realizing the promise of precision medicine. Full article

(This article belongs to the Special Issue Advanced Algorithms for Small-Molecule Therapeutics Development)

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26 pages, 1440 KB

Open AccessReview

Magnetic Fields in Cancer Therapy: Mechanistic Insights, Signaling Pathways, and Evidence from Clinical and In Vitro Studies

by Sadettin Berkay Sarli and Asiye Busra Boz Er

Pharmaceutics 2026, 18(6), 742; https://doi.org/10.3390/pharmaceutics18060742 - 15 Jun 2026

Viewed by 768

Abstract

Magnetic fields (MFs) represent an emerging modality in cancer therapy, encompassing static, low-frequency, pulsed, and nanoparticle-mediated alternating fields. These interventions have demonstrated the capacity to modulate proliferation, apoptosis, ferroptosis, migration, and epithelial-to-mesenchymal transition (EMT) in tumor cells, often through reactive oxygen species (ROS) [...] Read more.

Magnetic fields (MFs) represent an emerging modality in cancer therapy, encompassing static, low-frequency, pulsed, and nanoparticle-mediated alternating fields. These interventions have demonstrated the capacity to modulate proliferation, apoptosis, ferroptosis, migration, and epithelial-to-mesenchymal transition (EMT) in tumor cells, often through reactive oxygen species (ROS) modulation, ion channel regulation, membrane receptor dynamics, and lysosomal membrane permeabilization. Magnetic nanoparticle hyperthermia (MHT) has reached clinical application, showing promising outcomes in glioblastoma and prostate cancer, while pulsed electromagnetic fields (PEMFs) and magneto-mechanical approaches are under preclinical investigation. The mechanistic diversity of MFs allows synergistic combination with chemotherapy, radiotherapy, and immunotherapy. However, parameter sensitivity, field standardization, and long-term safety remain challenges. Here, we review mechanistic insights, signaling pathways, and experimental and clinical evidence for MF-based cancer therapies, highlighting translational potential and the need for rigorous optimization to realize clinical efficacy. Full article

(This article belongs to the Special Issue Magnetic Materials for Biomedical Applications)

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45 pages, 11152 KB

Open AccessReview

Molecular Docking of Natural Compounds as DPP-4 Inhibitors in Type 2 Diabetes: A Comprehensive Review

by Justyna Baranowska, Anna Kiss and Łukasz Szeleszczuk

Pharmaceutics 2026, 18(6), 741; https://doi.org/10.3390/pharmaceutics18060741 - 15 Jun 2026

Viewed by 664

Abstract

Dipeptidyl peptidase-4 (DPP-4) is an established therapeutic target in the treatment of type 2 diabetes mellitus (T2DM), primarily due to its role in regulating incretin activity and glucose homeostasis. Although clinically approved DPP-4 inhibitors are widely used, their moderate efficacy has driven the [...] Read more.

Dipeptidyl peptidase-4 (DPP-4) is an established therapeutic target in the treatment of type 2 diabetes mellitus (T2DM), primarily due to its role in regulating incretin activity and glucose homeostasis. Although clinically approved DPP-4 inhibitors are widely used, their moderate efficacy has driven the search for novel compounds with improved properties. In this context, natural products have attracted considerable attention as a source of structurally diverse and biologically active molecules. At the same time, molecular docking has emerged as a key computational tool for the identification and evaluation of potential DPP-4 inhibitors. This review summarizes and critically analyzes current molecular docking studies of natural compounds targeting DPP-4. Over 150 studies were evaluated with respect to docking methodologies, selection of protein structures, and validation strategies. The results reveal substantial variability in computational protocols. Frequently used protein structures include ligand-bound DPP-4 models such as 1X70 and 6B1E. Among the investigated compounds, flavonoids represent the most extensively studied class, followed by alkaloids, phenolics, terpenoids, and peptides. Despite numerous reports of favorable binding interactions within the DPP-4 active site, many studies rely solely on docking results without further validation. The limited use of molecular dynamics simulations and experimental assays highlights a significant gap in the current literature. Overall, while molecular docking provides valuable preliminary insights, improved standardization and integration with complementary approaches are essential to enhance the reliability and translational relevance of in silico findings. Full article

(This article belongs to the Special Issue Studies of Protein–Ligand Interactions in the Evaluation of the Biological Activity of Compounds)

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20 pages, 3086 KB

Open AccessArticle

Chemotherapeutic Loading and Delivery of Patient-Derived Extracellular Vesicles Are Influenced by Colorectal Cancer Disease Stage and Protein Corona

by Otman Saud, Dallal Blidi, Emily Hayes, Celine Souilhol, Rawan Maani, Alice Johnson, Keith Chapple and Nick Peake

Pharmaceutics 2026, 18(6), 740; https://doi.org/10.3390/pharmaceutics18060740 - 15 Jun 2026

Viewed by 746

Abstract

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with poor outcomes in advanced stages and significant limitations in current chemotherapy regimens due to systemic toxicity. Extracellular vesicles (EVs) have emerged as promising natural drug delivery vehicles, offering the potential [...] Read more.

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with poor outcomes in advanced stages and significant limitations in current chemotherapy regimens due to systemic toxicity. Extracellular vesicles (EVs) have emerged as promising natural drug delivery vehicles, offering the potential for targeted, less toxic therapies. This study investigates the feasibility of using autologous, patient-derived EVs as a delivery system for the chemotherapeutic agent doxorubicin, focusing on how disease stage and the EV protein corona influence loading and delivery efficiency. Methods: EVs were isolated from plasma and tissue samples of CRC patients at different disease stages, as well as from healthy controls, demonstrating successful isolation and characterisation of EVs, with distinct profiles across different sources. Results: Doxorubicin loading into EVs was significantly higher in CRC patient-derived EVs compared to healthy controls, and tissue-derived EVs yielded higher quantities of drug-loaded particles. Delivery of doxorubicin-loaded EVs to recipient CRC cell lines (SW480 and SW620) revealed that disease stage impacts both EV uptake and drug delivery, with late-stage EVs showing reduced uptake and delivery efficiency. The protein corona, known to coat circulating EVs, was found to influence drug loading and delivery. Pre-treatment of cell line-derived EVs with plasma proteins enhanced EV uptake but reduced doxorubicin loading and subsequent delivery, particularly when using plasma from healthy volunteers. Conclusions: These findings underscore the importance of EV source and protein corona composition in optimising drug delivery strategies. Our results suggest that autologous, patient-derived EVs hold potential as a targeted drug delivery system for CRC, but highlight the need for further optimisation of EV isolation, loading methods, and understanding of how disease progression affects EV functionality. This approach could ultimately reduce systemic toxicity and improve therapeutic outcomes for CRC patients. Full article

(This article belongs to the Special Issue Extracellular Vesicles for Targeted Delivery)

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19 pages, 5414 KB

Open AccessArticle

A CXCL10-Expressing Influenza Vector Induces Robust Adaptive Immunity Despite Strong Attenuation

by Olga Ozhereleva, Alina Mustafaeva, Anastasia Pulkina, Marina Plotnikova, Marina Shuklina, Anna-Polina Shurygina, Marina Stukova and Andrej Egorov

Pharmaceutics 2026, 18(6), 739; https://doi.org/10.3390/pharmaceutics18060739 - 14 Jun 2026

Viewed by 565

Abstract

Background/Objectives: Although influenza A viruses with partially truncated NS1 proteins are substantially attenuated and immunogenic due to enhanced innate immune activation; residual NS1-mediated antagonism of antiviral innate responses may support viral replication in the lower respiratory tract and constrain optimal immune responses. Strategies [...] Read more.

Background/Objectives: Although influenza A viruses with partially truncated NS1 proteins are substantially attenuated and immunogenic due to enhanced innate immune activation; residual NS1-mediated antagonism of antiviral innate responses may support viral replication in the lower respiratory tract and constrain optimal immune responses. Strategies to further improve their immunogenicity and protective efficacy by incorporating immunomodulatory cytokines, such as IL-2, have been successfully explored. Methods: Here, we extended this approach to chemokine expression by engineering an NS1-truncated PR8-based virus (PR8/NS124) to express the immunomodulatory chemokine CXCL10 from the NS segment and compared it with the parental vector. Results: The recombinant NS124_SS_CXCL10 virus replicated to high titers in embryonated chicken eggs and MDCK cells. In vivo, however, CXCL10 expression reduced viral replication in mouse lungs by ~10⁴-fold, resulting in a near-non-replicating phenotype. In contrast to the parental virus, the vector did not induce weight loss and exhibited a strongly attenuated phenotype. This effect was associated with altered innate immune signaling, including increased IRF7 expression and early induction of IFN-α responses in the lungs, together with modulation of TLR-dependent sensing pathways in the upper respiratory tract. Despite severely impaired replication, intranasal immunization induced antigen-specific T-cell responses comparable to those elicited by the parental vector. Following intraperitoneal immunization, when replication of both vectors was minimal, the CXCL10-expressing vector induced significantly higher frequencies of antigen-specific CD8⁺ and CD4⁺ effector-memory T cells. This was accompanied by enhanced antigen-specific T-cell recall responses in the lungs following intranasal challenge. Importantly, the CXCL10-expressing vector demonstrated protective efficacy comparable to that of the parental NS124 vector against heterologous H3N2 challenge while exhibiting an improved safety profile. Conclusions: These findings support the incorporation of CXCL10 as a strategy to improve the safety and T-cell immunogenicity of NS1-truncated influenza vectors. Full article

(This article belongs to the Special Issue Cutting-Edge Approaches to Smart Pharmaceutics and Vaccine Development)

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45 pages, 12445 KB

Open AccessReview

Flavonoids as Modulators of the p53–Bcl-2 Axis in Cancer: Molecular Mechanisms and Therapeutic Implications

by Julia Jankowska, Łukasz Szeleszczuk and Dariusz Maciej Pisklak

Pharmaceutics 2026, 18(6), 738; https://doi.org/10.3390/pharmaceutics18060738 - 14 Jun 2026

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Abstract

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and [...] Read more.

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

(This article belongs to the Special Issue Pharmaceutical Applications and Therapeutic Mechanisms of Substances from Plant Origin)

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41 pages, 3751 KB

Open AccessReview

Plant-Derived Polyphenols in Cancer Therapy: Bridging Molecular Mechanisms and Bioavailability Toward Clinical Translation

by Syed Arman Rabbani, Shrestha Sharma, Mohamed El-Tanani, Suman Khurana, Manita Saini, Monu Yadav, Rakesh Kumar and Yahia El-Tanani

Pharmaceutics 2026, 18(6), 737; https://doi.org/10.3390/pharmaceutics18060737 - 13 Jun 2026

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Abstract

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like [...] Read more.

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

(This article belongs to the Special Issue Natural Product-Based Anticancer Drug Development: From Molecular Mechanisms to Therapeutic Applications)

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19 pages, 33807 KB

Open AccessArticle

Porogen-Mediated Barrier Control in Multilayered Drug-Eluting Antibacterial Films: Comparative Evaluation of PEG, PVP, and PEOx

by Sergey G. Poroshin, Arkady S. Abdurashitov, Gleb B. Sukhorukov and Pavel I. Proshin

Pharmaceutics 2026, 18(6), 736; https://doi.org/10.3390/pharmaceutics18060736 - 13 Jun 2026

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Abstract

Background: Polymeric drug-eluting films are promising platforms for local antibacterial delivery, but their release profiles depend strongly on the permeability and morphology of the barrier layer. Here, the previously proposed concept of additively manufactured PLACE (Printed Layered Adjustable Cargo Encapsulation) coatings was extended [...] Read more.

Background: Polymeric drug-eluting films are promising platforms for local antibacterial delivery, but their release profiles depend strongly on the permeability and morphology of the barrier layer. Here, the previously proposed concept of additively manufactured PLACE (Printed Layered Adjustable Cargo Encapsulation) coatings was extended from "single orifice"-defined release toward porosity-assisted barrier control. Two conventional water-soluble porogens, polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), were compared with poly(2-ethyl-2-oxazoline) (PEOx), a hydrophilic polymer proposed as an alternative to PEG in biomedical formulations, but whose use as a leachable porogen has received little attention. Methods: Each porogen was introduced into the upper PLGA barrier of multilayer PLACE films. The resulting films were characterized for film formation, post-hydration morphology by SEM, release of methylene blue and vancomycin, and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Results/Conclusions: PEG was poorly compatible with PLGA and mainly produced surface-localized defects rather than a barrier with controlled permeability suitable for prolonged delivery. PVP K17 provided sustained release at 10 wt.%, whereas 20 wt.% PVP caused burst-dominated release and stronger morphological disruption. PEOx formed developed porosity at lower loading and produced release regimes ranging from several days to approximately two weeks. Vancomycin-loaded films containing 5 wt.% PEOx enabled near-complete release over two weeks while preserving film integrity and showed pronounced early anti-MRSA activity. These results identify porogen selection as a key formulation step and support PEOx as a useful porogen for early high-output antibacterial PLACE coatings. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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Pharmaceutics, Volume 18, Issue 6 (June 2026) – 133 articles

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