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Keywords = drug release profile

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27 pages, 2556 KB  
Article
Design and Characterization of Gold Nanorod Hyaluronic Acid Hydrogel Nanocomposites for NIR Photothermally Assisted Drug Delivery
by Alessandro Molinelli, Leonardo Bianchi, Elisa Lacroce, Zoe Giorgi, Laura Polito, Ada De Luigi, Francesca Lopriore, Francesco Briatico Vangosa, Paolo Bigini, Paola Saccomandi and Filippo Rossi
Gels 2026, 12(1), 88; https://doi.org/10.3390/gels12010088 (registering DOI) - 19 Jan 2026
Abstract
The combination of gold nanoparticles (AuNPs) with hydrogels has drawn significant interest in the design of smart materials as advanced platforms for biomedical applications. These systems endow light-responsiveness enabled by the AuNPs localized surface plasmon resonance (LSPR) phenomenon. In this study, we propose [...] Read more.
The combination of gold nanoparticles (AuNPs) with hydrogels has drawn significant interest in the design of smart materials as advanced platforms for biomedical applications. These systems endow light-responsiveness enabled by the AuNPs localized surface plasmon resonance (LSPR) phenomenon. In this study, we propose a nanocomposite hydrogel in which gold nanorods (AuNRs) are included in an agarose–carbomer–hyaluronic acid (AC-HA)-based hydrogel matrix to study the correlation between light irradiation, local temperature increase, and drug release for potential light-assisted drug delivery applications. The gel is obtained through a facile microwave-assisted polycondensation reaction, and its properties are investigated as a function of both the hyaluronic acid molecular weight and ratio. Afterwards, AuNRs are incorporated in the AC-HA formulation, before the sol–gel transition, to impart light-responsiveness and optical properties to the otherwise inert polymeric matrix. Particular attention is given to the evaluation of AuNRs/AC-HA light-induced heat generation and drug delivery performances under near-infrared (NIR) laser irradiation in vitro. Spatiotemporal thermal profiles and high-resolution thermal maps are registered using fiber Bragg grating (FBG) sensor arrays, enabling accurate probing of maximum internal temperature variations within the composite matrix. Lastly, using a high-steric-hindrance protein (BSA) as a drug mimetic, we demonstrate that moderate localized heating under short-time repeated NIR exposure enhances the release from the nanocomposite hydrogel. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Repair: Innovations and Applications)
22 pages, 6931 KB  
Article
Biopolymer Casein–Pullulan Coating of Fe3O4 Nanocomposites for Xanthohumol Encapsulation and Delivery
by Nikolay Zahariev, Dimitar Penkov, Radka Boyuklieva, Plamen Simeonov, Paolina Lukova, Raina Ardasheva and Plamen Katsarov
Polymers 2026, 18(2), 256; https://doi.org/10.3390/polym18020256 - 17 Jan 2026
Viewed by 68
Abstract
Introduction: Magnetic nanoparticles are widely investigated as multifunctional platforms for drug delivery and theranostic applications, yet their biomedical implementation is hindered by aggregation, limited colloidal stability, and insufficient biocompatibility. Hybrid biopolymer coatings can mitigate these issues while supporting drug incorporation. Aim: This study [...] Read more.
Introduction: Magnetic nanoparticles are widely investigated as multifunctional platforms for drug delivery and theranostic applications, yet their biomedical implementation is hindered by aggregation, limited colloidal stability, and insufficient biocompatibility. Hybrid biopolymer coatings can mitigate these issues while supporting drug incorporation. Aim: This study aimed to develop casein–pullulan-coated Fe3O4 nanocomposites loaded with xanthohumol, enhancing stability and enabling controlled release for potential theranostic use. Methods: Fe3O4 nanoparticles were synthesized through co-precipitation and incorporated into a casein–pullulan matrix formed via polymer complexation and glutaraldehyde crosslinking. A 32 full factorial design evaluated the influence of casein:pullulan ratio and crosslinker concentration on physicochemical performance. Nanocomposites were characterized for size, zeta potential, morphology, composition, and stability, while drug loading, encapsulation efficiency, and release profiles were determined spectrophotometrically. Molecular docking was performed to examine casein–pullulan interactions. Results: Uncoated Fe3O4 nanoparticles aggregated extensively, displaying mean sizes of ~292 nm, zeta potential of +80.95 mV and high polydispersity (PDI above 0.2). Incorporation into the biopolymer matrix improved colloidal stability, yielding particles of ~185 nm with zeta potentials near –35 mV. TEM and SEM confirmed spherical morphology and uniform magnetic core incorporation. The optimal formulation, consisting of a 1:1 casein:pullulan ratio with 1% glutaraldehyde, achieved 5.7% drug loading, 68% encapsulation efficiency, and sustained release of xanthohumol up to 84% over 120 h, fitting Fickian diffusion (Korsmeyer–Peppas R2 = 0.9877, n = 0.43). Conclusions: Casein–pullulan hybrid coatings significantly enhance Fe3O4 nanoparticle stability and enable controlled release of xanthohumol, presenting a promising platform for future targeted drug delivery and theranostic applications. Full article
(This article belongs to the Special Issue Engineered Polymeric Particles for Next-Generation Nanomedicine)
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28 pages, 2829 KB  
Article
Correlation of Polymer–drug Composition with Micelle Properties, Performance, and Cytotoxicity for the Oligoelectrolyte-mediated pH-triggered Release of Hydrophobic Drugs
by Md. Saddam Hussain, Riya Khetan, Hugo Albrecht, Marta Krasowska and Anton Blencowe
Polymers 2026, 18(2), 247; https://doi.org/10.3390/polym18020247 - 16 Jan 2026
Viewed by 101
Abstract
Polymeric micelles have the potential to improve the efficacy and safety of drug delivery by improving drug solubility, enhancing bioaccumulation and reducing off-target toxicity. Despite excellent safety profiles, a major limitation with polymeric micelles is their inability to rapidly release their payload once [...] Read more.
Polymeric micelles have the potential to improve the efficacy and safety of drug delivery by improving drug solubility, enhancing bioaccumulation and reducing off-target toxicity. Despite excellent safety profiles, a major limitation with polymeric micelles is their inability to rapidly release their payload once they have reached their target, leading to the inadequate delivery of therapeutic doses. To address this limitation, we have developed a novel strategy to impart pH-responsiveness in non-responsive micelles through the co-encapsulation of oligoelectrolytes with drugs. Herein, we investigate the influence of copolymer composition and drug identity in combination with oligoelectrolyte—oligo(2-vinyl pyridine) (OVP)—loading on pH-triggered drug release from micelles and their cytotoxicity. A library of OVP-loaded micelles was prepared using conventional and well-established non-responsive block copolymers. Dynamic light scattering (DLS) was used to monitor the changes in the micelles as a function of pH. Regardless of the copolymer composition, an abrupt decrease in the hydrodynamic diameter (Dh) was observed as the pH was reduced due to OVP expulsion from the core, which was also confirmed by release studies. In general, co-encapsulation of OVP and model drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX), and 7-ethyl-10-hydroxycamptothecin (SN38)) in the micelles provided good to excellent encapsulation efficiency percentage (EE%) values. In vitro studies revealed the pH triggered release of drugs from the OVP-loaded micelles regardless of the drug identity, which increased as the OVP loading increased. This general behaviour was observed in all cases, largely independent of the copolymer composition, albeit with subtle differences in the release profile for different drugs. Compared to their blank counterparts, the drug-loaded micelles displayed a slight increase in cytotoxicity against a panel of cancer cell lines, in a dose dependent manner. However, drug- and OVP-loaded micelles displayed a significant increase in cytotoxicity (up to 8-fold increase) that was independent of the copolymer composition. These results demonstrate the versatility of the oligoelectrolyte-mediated approach to furnish non-responsive micelles with a pH-trigger that allows the rapid release of drugs, regardless of the micelle composition or the drug identity. Full article
(This article belongs to the Section Polymer Applications)
22 pages, 3229 KB  
Article
Antitumor Activity of All-Trans Retinoic Acid and Curcumin-Loaded BSA Nanoparticles Against U87 Glioblastoma Cells
by Ceyda Sonmez, Aleyna Baltacioglu, Julide Coskun, Gulen Melike Demirbolat, Ozgul Gok and Aysel Ozpinar
Life 2026, 16(1), 131; https://doi.org/10.3390/life16010131 - 15 Jan 2026
Viewed by 168
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor characterized by invasive growth, intrinsic drug resistance, and the presence of the blood–brain barrier. All of these features make treatment extremely challenging and underscore the need for developing effective combination strategies and advanced drug delivery [...] Read more.
Glioblastoma (GBM) is a highly aggressive brain tumor characterized by invasive growth, intrinsic drug resistance, and the presence of the blood–brain barrier. All of these features make treatment extremely challenging and underscore the need for developing effective combination strategies and advanced drug delivery systems. This study aimed to develop a bovine serum albumin (BSA) nanoparticle (NP)-based delivery system to overcome the poor bioavailability and pharmacokinetic limitations of two potent anti-tumor agents, all-trans retinoic acid (ATRA) and curcumin (CURC), and to evaluate their antitumor activity in U87-MG GBM cells. Drug-free and ATRA/CURC-loaded BSA-NPs were synthesized using an optimized desolvation method and characterized in terms of particle size, polydispersity index, morphology, drug encapsulation efficiency, and release behavior. The cytotoxic, anti-migratory, and pro-apoptotic effects of the NPs on U87-MG GBM cells were assessed using real-time proliferation and migration assays and Annexin V/PI staining followed by flow cytometry. Collectively, the findings indicated that the co-delivery of ATRA and CURC using BSA-NPs showed enhanced antiproliferative, antimigratory, and pro-apoptotic effects. With its controlled release profile, high loading capacity, and favorable nanoscale dimensions, the ATRA-CURC-BSA–NP system represents a promising nanoplatform for GBM therapy that warrants further in vivo investigation. To the best of our knowledge, this is the first study demonstrating the inhibition of glioblastoma cell growth through the co-delivery of all-trans retinoic acid and curcumin using a bovine serum albumin-based nanoparticle system. Full article
(This article belongs to the Section Pharmaceutical Science)
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25 pages, 3149 KB  
Article
Design and Factorial Optimization of Curcumin and Resveratrol Co-Loaded Lipid Nanocarriers for Topical Delivery
by Daniela Pastorim Vaiss, Débora Cristine Chrisostomo Dias, Virginia Campello Yurgel, Fernanda Beatriz Venturi Araujo, Ledilege Cucco Porto, Janaina Fernandes de Medeiros Burkert, Marcelo Augusto Germani Marinho, Daza de Moraes Vaz Batista Filgueira and Cristiana Lima Dora
Pharmaceutics 2026, 18(1), 109; https://doi.org/10.3390/pharmaceutics18010109 - 15 Jan 2026
Viewed by 204
Abstract
Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to [...] Read more.
Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to develop a topical formulation with antioxidant and anti-inflammatory properties. Methods: NLCs were produced via hot emulsification followed by high-pressure homogenization, and their physicochemical characteristics, drug content, stability, release profile, antioxidant activity, skin delivery, and cellular compatibility were evaluated. Results: The optimized formulation exhibited an average particle size of approximately 300 nm, a polydispersity index below 0.3, and high drug loading for both compounds. Stability studies over 90 days revealed no significant changes in physicochemical parameters, confirming the formulation’s robustness. In vitro release assays demonstrated sustained release of both actives, with 58.6 ± 2.9% of CUR and 97 ± 3% of RESV released after 72 h. Antioxidant activity, assessed by the DPPH and ABTS assays, showed concentration-dependent radical-scavenging effects, indicating antioxidant potential. Skin permeation/retention experiments using porcine skin showed enhanced retention of CUR and RESV within the tissue, with no detectable permeation, indicating suitability for topical delivery. In addition, in vitro cell assays using human keratinocytes showed concentration-dependent responses and acceptable cellular compatibility. Conclusions: Overall, this study demonstrates the successful application of nanotechnology and experimental design to develop stable and efficient lipid-based nanocarriers containing natural polyphenol for topical therapy targeting oxidative and inflammatory skin disorders. Full article
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44 pages, 10841 KB  
Article
Study on Dual-Targeted Liposomes Containing Curcumin-Copper Chelate in the Treatment of Triple-Negative Breast Cancer
by Lina Wu, Xueli Guo and Pan Guo
Pharmaceuticals 2026, 19(1), 135; https://doi.org/10.3390/ph19010135 - 13 Jan 2026
Viewed by 178
Abstract
Background: Triple-negative breast cancer (TNBC) remains primarily treated with chemotherapy due to the lack of effective therapeutic targets, but this approach carries significant systemic toxicity and a high risk of drug resistance. Curcumin (Cur), despite its multifaceted antitumor activity, faces limitations in [...] Read more.
Background: Triple-negative breast cancer (TNBC) remains primarily treated with chemotherapy due to the lack of effective therapeutic targets, but this approach carries significant systemic toxicity and a high risk of drug resistance. Curcumin (Cur), despite its multifaceted antitumor activity, faces limitations in clinical application due to poor water solubility and weak targeting properties. This study aims to develop a folate/mitochondria dual-targeted curcumin–copper chelate liposome (Cu-Cur DTLPs) formulation that enables copper accumulation within tumor cells and induces copper-mediated cell death, thereby providing an effective and relatively low-toxicity therapeutic strategy for triple-negative breast cancer. Methods: Curcumin–copper chelates (Cu-Cur) were first synthesized and characterized using mass spectrometry, NMR, and infrared spectroscopy. Subsequently, dual-targeted liposomes (Cu-Cur DTLPs) were prepared via the thin-film dispersion method, with systematic evaluation of particle size, zeta potential, encapsulation efficiency, and in vitro release profiles. In vitro cytotoxicity was assessed against 4T-1 and MDA-MB-231 cells using the MTT assay. In a 4T-1 tumor-bearing BALB/c mouse model, comprehensive evaluation of targeting efficiency, antitumor efficacy, and mechanisms of action was conducted via in vivo imaging, tumor volume monitoring, immunohistochemistry (detecting FDX1 and DLAT proteins), and TUNEL staining. Results: Cu-Cur DTLPs with a uniform particle size of approximately 104.4 nm were successfully synthesized. In vitro and in vivo studies demonstrated that compared to free curcumin and conventional liposomes, Cu-Cur DTLPs significantly enhanced drug accumulation in tumor tissues and exhibited effective tumor growth inhibition. Mechanistic studies confirmed that this formulation specifically accumulates copper ions within tumor cells, upregulates FDX1, promotes DLAT oligomerization, and induces mitochondrial dysfunction, thereby driving copper death. TUNEL staining ruled out apoptosis as the primary mechanism. Safety evaluation revealed no significant toxicity in major organs. Conclusions: The Cu-Cur DTLPs developed in this study effectively induce copper-mediated death in TNBC through a dual-targeted delivery system, significantly enhancing antitumor activity with favorable safety profiles. This establishes a highly promising novel nanotherapeutic strategy for TNBC treatment. Full article
(This article belongs to the Section Medicinal Chemistry)
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15 pages, 5958 KB  
Article
Tunable Drug Release from 3D-Printed Bilayer Tablets: Combining Hot-Melt Extrusion and Fused Deposition Modeling
by Sangyeob Lee, Eon Soo Song, Eungyeop Lee, Gabin Kwon and Dong Wuk Kim
Polymers 2026, 18(2), 210; https://doi.org/10.3390/polym18020210 - 13 Jan 2026
Viewed by 241
Abstract
This study presents a practical and tunable 3D printing-based approach for manufacturing oral controlled-release bilayer tablets by modulating drug release solely through layer ratio control within a single dosage form. Theophylline-loaded filaments were prepared via hot-melt extrusion (HME) using Kollicoat® IR or [...] Read more.
This study presents a practical and tunable 3D printing-based approach for manufacturing oral controlled-release bilayer tablets by modulating drug release solely through layer ratio control within a single dosage form. Theophylline-loaded filaments were prepared via hot-melt extrusion (HME) using Kollicoat® IR or hydroxypropyl cellulose as polymer matrices. The mechanical properties of the manufactured filaments were evaluated and compared with commercial filaments to confirm their suitability for fused deposition modeling (FDM) printing. Physicochemical characterization using scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy indicated partial crystallinity and molecular dispersion of the drug within the polymer matrices. Using a dual-nozzle FDM 3D printer, five bilayer tablets composed of two drug-loaded filaments at different layer ratios were successfully fabricated without altering formulation composition or processing conditions. Drug release studies revealed distinct dissolution behaviors that were strongly dependent on the bilayer composition. Overall, this study demonstrates that controlled drug release can be effectively achieved through geometric modulation of bilayer structures using a combined HME–FDM 3D printing approach, providing a practical platform for personalized oral drug delivery without increasing formulation complexity. Full article
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26 pages, 4325 KB  
Article
Pentamidine-Functionalized Polycaprolactone Nanofibers Produced by Solution Blow Spinning for Controlled Release in Cutaneous Leishmaniasis Treatment
by Nerea Guembe-Michel, Paul Nguewa and Gustavo González-Gaitano
Polymers 2026, 18(2), 170; https://doi.org/10.3390/polym18020170 - 8 Jan 2026
Viewed by 222
Abstract
Leishmaniasis, a widespread, neglected infectious disease with limited effective treatments and increasing drug resistance, demands innovative therapeutic approaches. In this study, we report the fabrication of pentamidine (PTM)-loaded polycaprolactone (PCL) nanofibers using solution blow spinning (SBS) as a potential topical delivery system for [...] Read more.
Leishmaniasis, a widespread, neglected infectious disease with limited effective treatments and increasing drug resistance, demands innovative therapeutic approaches. In this study, we report the fabrication of pentamidine (PTM)-loaded polycaprolactone (PCL) nanofibers using solution blow spinning (SBS) as a potential topical delivery system for cutaneous leishmaniasis (CL). Homogeneous PCL fiber mats were produced using a simple SBS set-up with a commercial airbrush after optimizing several working parameters. Drug release studies demonstrated sustained PTM release profile over time, which was mechanistically modeled by utilizing the complete nanofiber diameter distribution, obtained from SEM analysis of the blow-spun material. FTIR and XRD analyses were performed to investigate the drug–polymer interactions, revealing molecularly dispersed PTM at low-proportion drug/polymers and partial crystallinity at high loadings. The released PTM exhibited significant leishmanicidal activity against Leishmania major promastigotes. Biological investigations showed that SBS-formulated PTM treatment was consistent with the downregulation of parasite genes involved in cell division and DNA replication (cycA, cyc6, pcna, top2, mcm4) and upregulation of the drug response gene (prp1). The controlled delivery of PTM within SBS-fabricated PCL nanofibers provides an effective therapeutic approach to tackle CL and, through the incorporation of additional drugs, could be extended to address a broader range of cutaneous infections. Full article
(This article belongs to the Special Issue Fiber Spinning Technologies and Functional Polymer Fiber Development)
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12 pages, 1200 KB  
Article
In Vitro Evaluation of the Antimicrobial Properties of Chitosan–Vancomycin Coatings on Grade 4 Titanium Discs: A Preliminary Study
by João M. Pinto, Liliana Grenho, Susana J. Oliveira, Manuel A. Sampaio-Fernandes, Maria Helena Fernandes, Maria Helena Figueiral and Maria Margarida Sampaio-Fernandes
Coatings 2026, 16(1), 75; https://doi.org/10.3390/coatings16010075 - 8 Jan 2026
Viewed by 243
Abstract
Peri-implant infections pose a significant challenge in dental implantology. This study aimed to develop and characterize a chitosan–vancomycin coating for titanium surfaces, focusing on drug loading, release kinetics, antimicrobial performance, and cytocompatibility. Grade 4 titanium discs were coated with a chitosan film using [...] Read more.
Peri-implant infections pose a significant challenge in dental implantology. This study aimed to develop and characterize a chitosan–vancomycin coating for titanium surfaces, focusing on drug loading, release kinetics, antimicrobial performance, and cytocompatibility. Grade 4 titanium discs were coated with a chitosan film using the dip-coating technique and subsequently loaded with vancomycin through immersion in an aqueous solution. Coating morphology was examined by scanning electron microscopy (SEM). Vancomycin loading was quantified by spectrophotometry, and release kinetics were monitored over 144 h (6-day). Antimicrobial activity was assessed through agar diffusion assays against Staphylococcus aureus. Cytocompatibility was evaluated using human mesenchymal stem cells (hMSCs), whose metabolic activity, adhesion, and morphology were assessed over a 19-day culture period by resazurin assay and SEM. SEM analysis revealed a uniformly distributed, smooth, and crack-free chitosan film, which remained stable after drug loading. The coating exhibited a biphasic release profile, characterized by an initial burst followed by sustained release over six days, which maintained antimicrobial activity, as confirmed by inhibition zones. hMSCs adhered and proliferated on the coated surfaces, displaying normal morphology despite a transient reduction in metabolic activity on vancomycin-containing films. These findings support the potential of chitosan–vancomycin coatings as localized antimicrobial strategies for implant applications, warranting further in vivo and mechanical evaluations. Full article
(This article belongs to the Special Issue Films and Coatings with Biomedical Applications)
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14 pages, 1038 KB  
Article
Designing Poly(vinyl formal) Membranes for Controlled Diclofenac Delivery: Integrating Classical Kinetics with GRNN Modeling
by Igor Garcia-Atutxa and Francisca Villanueva-Flores
Appl. Sci. 2026, 16(2), 562; https://doi.org/10.3390/app16020562 - 6 Jan 2026
Viewed by 131
Abstract
Controlled-release systems must translate material design choices into predictable pharmacokinetic (PK) profiles, yet purely mechanistic or purely data-driven models often underperform when tuning complex polymer networks. Here, we develop tunable poly(vinyl formal) membranes (PVFMs) for diclofenac delivery and integrate classical kinetic analysis with [...] Read more.
Controlled-release systems must translate material design choices into predictable pharmacokinetic (PK) profiles, yet purely mechanistic or purely data-driven models often underperform when tuning complex polymer networks. Here, we develop tunable poly(vinyl formal) membranes (PVFMs) for diclofenac delivery and integrate classical kinetic analysis with a Generalized Regression Neural Network (GRNN) to connect formulation variables to release behavior and PK-relevant targets. PVFMs were synthesized across a gradient of crosslink densities by varying HCl content; diclofenac release was quantified under standardized conditions with geometry and dosing rigorously controlled (thickness, effective area, surface-area-to-volume ratio, and areal drug loading are reported to ensure reproducibility). Release profiles were fitted to Korsmeyer–Peppas, zero-order, first-order, Higuchi, and hyperbolic tangent models, while a GRNN was trained on material descriptors and time to predict cumulative release and flux, including out-of-sample conditions. Increasing crosslink density monotonically reduced swelling, areal release rate, and overall release efficiency (strong linear trends; r ≈ 0.99) and shifted transport from anomalous to Super Case II at the highest crosslinking. Classical models captured regime transitions but did not sustain high accuracy across the full design space; in contrast, the GRNN delivered superior predictive performance and generalized to conditions absent from training, enabling accurate interpolation/extrapolation of release trajectories. Beyond prior work, we provide a material-to-PK design map in which crosslinking, porosity/tortuosity, and hydrophobicity act as explicit “knobs” to shape burst, flux, and near-zero-order behavior, and we introduce a hybrid framework where mechanistic models guide interpretation while GRNN supplies robust, data-driven prediction for formulation selection. This integrated PVFM–GRNN approach supports rational design and quality control of controlled-release devices for diclofenac and is extendable to other therapeutics given appropriate descriptors and training data. Full article
(This article belongs to the Section Materials Science and Engineering)
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28 pages, 1526 KB  
Review
Applications of Exosomes in Female Medicine: A Systematic Review of Molecular Biology, Diagnostic and Therapeutic Perspectives
by Heidi Mariadas, Jie-Hong Chen and Kuo-Hu Chen
Int. J. Mol. Sci. 2026, 27(1), 504; https://doi.org/10.3390/ijms27010504 - 3 Jan 2026
Viewed by 466
Abstract
Exosomes are nanoscale extracellular vesicles that mediate intercellular communication by transporting microRNAs, proteins, and lipids. Generated through Endosomal Sorting Complex Required for Transport (ESCRT)-dependent mechanisms or ESCRT-independent pathways, exosomes are released when multivesicular bodies fuse with the plasma membrane. The ESCRT-dependent pathway involves [...] Read more.
Exosomes are nanoscale extracellular vesicles that mediate intercellular communication by transporting microRNAs, proteins, and lipids. Generated through Endosomal Sorting Complex Required for Transport (ESCRT)-dependent mechanisms or ESCRT-independent pathways, exosomes are released when multivesicular bodies fuse with the plasma membrane. The ESCRT-dependent pathway involves sequential protein complexes (ESCRT-0, I, II, III) that recognize and sort ubiquitinated cargo, induce membrane budding, and facilitate vesicle scission. In contrast, the ESCRT-independent pathway relies on membrane lipids such as ceramide and proteins like tetraspanins (CD9, CD63, CD81) to promote vesicle formation without ESCRT machinery. Furthermore, post-translational modifications, including ubiquitination, sumoylation, and phosphorylation, further serve as molecular switches, modulating the affinity of ESCRT complexes or cargo proteins for membrane domains and affecting ILV formation rates. In reproductive medicine, exosomes regulate oocyte maturation, embryo–endometrial crosstalk, placental development, and maternal–fetal communication. Altered exosomal signaling contributes to obstetric complications, including preeclampsia, gestational diabetes mellitus, and preterm birth, whereas distinct exosomal miRNA signatures serve as potential diagnostic biomarkers. In gynecology, dysregulated exosomes are implicated in endometriosis, polycystic ovary syndrome, premature ovarian insufficiency, and gynecological malignancies. In contrast, mesenchymal stem cell-derived exosomes show therapeutic promise in restoring ovarian function and enhancing fertility outcomes. The distinctive molecular profiles of circulating exosomes enable minimally invasive diagnosis, while their biocompatibility and ability to cross biological barriers position them as vehicles for targeted drug delivery. Characterization of accessible data provides non-invasive opportunities for disease monitoring. However, clinical translation faces challenges, including standardization of isolation protocols, establishment of reference ranges for biomarkers, and optimization of therapeutic dosing. This review summarizes exosome biogenesis, characterization methods, physiological functions, and clinical applications in obstetrics and gynecology, with an emphasis on their diagnostic and therapeutic potential. Future directions include large-scale biomarker validation studies, engineering approaches to enhance exosome targeting, and integration with precision medicine platforms to advance personalized reproductive healthcare. Full article
(This article belongs to the Special Issue Exosomes—3rd Edition)
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22 pages, 4387 KB  
Article
The Optimal Amount of PAMAM G3 Dendrimer in Polyurethane Matrices Makes Them a Promising Tool for Controlled Drug Release
by Magdalena Zaręba, Magdalena Zuzanna Twardowska, Paweł Błoniarz, Jaromir B. Lechowicz, Jakub Czechowicz, Dawid Łysik, Magdalena Rzepna and Łukasz Stanisław Uram
Polymers 2026, 18(1), 135; https://doi.org/10.3390/polym18010135 - 1 Jan 2026
Viewed by 485
Abstract
Systemic anticancer therapy causes a number of side effects; therefore, local drug release devices may play an important role in this area. In this study, we developed polyurethane-dendrimer foams containing different amounts of third-generation poly (amidoamine) dendrimers (PAMAM G3) to evaluate their ability [...] Read more.
Systemic anticancer therapy causes a number of side effects; therefore, local drug release devices may play an important role in this area. In this study, we developed polyurethane-dendrimer foams containing different amounts of third-generation poly (amidoamine) dendrimers (PAMAM G3) to evaluate their ability to encapsulate and release the model anticancer drug doxorubicin (DOX), as well as their biocompatibility and effectiveness against normal and cancer cells in vitro. PU–PAMAM foams containing 10–50 wt% PAMAM G3 were prepared using glycerin-based polyether polyol and castor oil as co-components. Structural and rheological analyses revealed that foams containing up to 20 wt% PAMAM G3 exhibited a well-developed porous structure, while higher dendrimer loadings (≥30 wt%) led to irregular cell shapes, pore coalescence, and thinning of cell walls, and indicated a gradual loss of structural integrity. Rheological creep–recovery measurements confirmed the structural findings: moderate PAMAM G3 incorporation (≤20 wt%) increased both the instantaneous and delayed elastic modulus (E1 ≈ 130–140 kPa; E2 ≈ 80 kPa) and enhanced elastic recovery, reflecting improved cross-link density and foam stability. Higher dendrimer contents (30–50 wt%) caused a decline in these parameters and higher viscoelastic compliance, indicating a softer, less stable structure. The DOX loading capacity and encapsulation efficiency increased with PAMAM G3 content, reaching maximum values of 35% and 51% for 30–40 wt% PAMAM G3, respectively. However, the most sustained DOX release profiles were observed for matrices containing 20 wt% PAMAM G3. Analysis of cumulative release and kinetic modeling revealed a transition from diffusion-controlled release at low PAMAM contents to burst-dominated release at higher dendrimer loadings. Importantly, matrices containing 10–20 wt% PAMAM G3 also indicated selective anticancer action against squamous cell carcinoma (SCC-15) compared to non-cancerous human keratinocytes (HaCaT). Moreover, the DOX they released effectively destroyed cancer cells. Overall, PU–PAMAM foams containing 10–20 wt% PAMAM G3 provide the most balanced combination of structural stability, controlled drug release, and cytocompatibility. These materials therefore represent a promising platform as passive carriers in drug delivery systems (DDSs), such as local implants, anticancer patches, or bioactive wound dressings. Full article
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26 pages, 3111 KB  
Article
Preclinical Investigation of PLGA Nanocapsules and Nanostructured Lipid Carriers for Organoselenium Delivery: Comparative In Vitro Toxicological Profile and Anticancer Insights
by Bianca Costa Maia-do-Amaral, Taís Baldissera Pieta, Luisa Fantoni Zanon, Gabriele Cogo Carneosso, Laísa Pes Nascimento, Nayra Salazar Rocha, Bruna Fracari do Nascimento, Letícia Bueno Macedo, Tielle Moraes de Almeida, Oscar Endrigo Dorneles Rodrigues, Scheila Rezende Schaffazick, Clarice Madalena Bueno Rolim and Daniele Rubert Nogueira-Librelotto
Pharmaceutics 2026, 18(1), 57; https://doi.org/10.3390/pharmaceutics18010057 - 31 Dec 2025
Viewed by 433
Abstract
Background/Objectives: Cancer is a major health concern involving abnormal cell growth. Combining anticancer agents can enhance efficacy and overcome resistance by targeting multiple pathways and creating synergistic effects. Methods: This study used in silico approaches to evaluate the physicochemical and pharmacokinetic profiles of [...] Read more.
Background/Objectives: Cancer is a major health concern involving abnormal cell growth. Combining anticancer agents can enhance efficacy and overcome resistance by targeting multiple pathways and creating synergistic effects. Methods: This study used in silico approaches to evaluate the physicochemical and pharmacokinetic profiles of the innovative organoselenium nucleoside analog Di3a, followed by the design of two nanocarriers. Di3a-loaded PLGA nanocapsules and nanostructured lipid carriers based on compritol were prepared and evaluated alone and combined with doxorubicin (DOX) and docetaxel (DTX) for a synergistic effect. Results: Di3a subtly violated some of Lipinski’s rules, but still showed suitable pharmacokinetic properties. Both nanoparticles presented nanometric size, negative zeta potential and polydispersity index values < 0.20. Hemolysis assay suggested a pH-dependent pattern conferred by the surfactant 77KL, and evidenced the biocompatibility of the formulations, aligning with the results observed in the nontumor L929 cell line. The lack of drug release studies under varying pH conditions constitutes a limitation and warrants further investigation to validate the pH-responsive properties of the nanocarriers. MTT assay revealed that both formulations exhibited significant cytotoxic effects in the A549 cell line. However, neither formulation exhibited marked toxicity toward NCI/ADR-RES, a resistant tumor cell line. Conversely, when combined with DOX or DTX, the treatments were able to sensitize these resistant cells, achieving expressive synergistic antitumor activity. Conclusions: Despite the limitations in the in silico studies, the study highlights the potential of combining the proposed nanocarriers with conventional antitumor drugs to sensitize multidrug-resistant cancer cells and emphasizes the safety of the developed nanoformulations. Full article
(This article belongs to the Special Issue Application of PLGA Nanoparticles in Cancer Therapy)
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22 pages, 6766 KB  
Article
Zn–IMP 3D Coordination Polymers for Drug Delivery: Crystal Structure and Computational Studies
by Hafiz Zeshan Aqil, Yanhong Zhu, Masooma Hyder Khan, Yaqoot Khan, Beenish Sandhu, Muhammad Irfan and Hui Li
Polymers 2026, 18(1), 119; https://doi.org/10.3390/polym18010119 - 31 Dec 2025
Viewed by 349
Abstract
Coordination polymers (CPs) are garnering attention in the field of medicine day by day. The goal is to develop a CP with biosafe and environment-friendly characteristics. Herein, we report two such novel 3D coordination polymers of zinc-inosine-5′-monophosphate (Zn-IMP) and bpe/azpy (as linkers) which [...] Read more.
Coordination polymers (CPs) are garnering attention in the field of medicine day by day. The goal is to develop a CP with biosafe and environment-friendly characteristics. Herein, we report two such novel 3D coordination polymers of zinc-inosine-5′-monophosphate (Zn-IMP) and bpe/azpy (as linkers) which were engineered as metal–organic frameworks that can be used as drug carriers for hydroxyurea (HU). We employed SCXRD, PXRD, solid-state CD, FTIR and TGA for crystal structure characterizations; the results achieved 3D coordination polymers which contain a P21 space group with chiral distorted tetrahedral geometry. Solution phase studies like UV–vis and CD were carried out to understand mechanistic pathways for interaction and chirality, respectively. We have also performed computational studies to evaluate the drug delivery capacity of both 3D CPs. Molecular docking and multi-pH molecular dynamics (MD) quantify that HU binds more strongly with CP−1 (ΔG =−10.87 ± 0.12) as compared to CP−2 (ΔG = −7.59 ± 0.26 kcal·mol−1), at normal and basic pH. MD simulation analysis indicated that a more compact and rigid cavity is observed by CP−1 as compared to CP−2 at physiological pH. Across acidic pH, for CP−1 the ligand RMSD increases markedly and U becomes slightly less negative, which indicated partial loss of contacts, thus releasing drugs in a tumor-like environment more easily. These result showed that CP−1 offers stronger binding, higher structural stability and a more pronounced pH-responsive release profile than CP−2, making CP-1 more promising candidate for targeted HU drug delivery, while CP−2 may serve as a weaker-binding, faster-release complement. Full article
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13 pages, 3265 KB  
Article
Waterproof Fabric with Copper Ion-Loaded Multicompartmental Nanoparticle Coatings for Jellyfish Repellency
by Bo Wang, Muzi Yang, Ruiqian Yao, Haixia Zhao, Dengguang Yu, Lin Du, Shuaijun Zou and Yuanjie Zhu
Pharmaceutics 2026, 18(1), 47; https://doi.org/10.3390/pharmaceutics18010047 - 30 Dec 2025
Viewed by 263
Abstract
Background: Effective prevention of jellyfish stings is crucial for human safety during marine activities. Traditional protective methods are often limited in terms of coverage area and duration of protection; Methods: This study designed and tested a novel jellyfish-repellent textile by coating waterproof [...] Read more.
Background: Effective prevention of jellyfish stings is crucial for human safety during marine activities. Traditional protective methods are often limited in terms of coverage area and duration of protection; Methods: This study designed and tested a novel jellyfish-repellent textile by coating waterproof polyester fabric with copper ion-loaded multicompartmental nanoparticles, which repel jellyfish by disrupting their cellular membranes and physiological functions. The nanoparticles were synthesized to enable spatial separation of components, enhance stability, and allow controlled copper ion release. They were applied to the fabric in one step via high-voltage electrostatic spray technology, followed by characterization using SEM and FT-IR. The copper sulfate release profile and nanoparticle adhesion were analyzed. Jellyfish-repellent efficacy was evaluated, along with biocompatibility tests including skin sensitization (Magnusson and Kligman method), skin irritation (Draize test), and cytotoxicity (MTT assay on L929 cells and human dermal fibroblasts). Results: SEM confirmed the formation of uniform multicompartmental nanoparticles with sizes ranging from 2.28 to 3.15 μm. FT-IR verified successful anchoring of Cu2+ ions to fabric fibers through coordination with hydroxyl groups. Drug release tests demonstrated water-triggered controlled release of copper ions lasting over 168 h, with nanoparticle retention rates exceeding 70% on all fabrics. The textile showed significant effectiveness in repelling jellyfish. Moreover, no apparent sensitization, irritation, or cytotoxicity was observed. Conclusions: A novel jellyfish-repellent textile was successfully developed using copper ion-loaded multicompartmental nanoparticles. This textile provides a promising solution for preventing jellyfish stings and contributes to the advancement of protective gear for marine activities. Full article
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