Pharmaceutics最新文献

{"title":"Synthesis and In Vitro Evaluation of a Scandium-44 Radiolabeled Nanobody as a PD-L1 PET Imaging Probe.","authors":"Viktoria E Krol, Aditya Bansal, Manasa Kethamreddy, Jason R Ellinghuysen, Daniel J Vail, Fabrice Lucien-Matteoni, Haidong Dong, Sean S Park, Mukesh K Pandey","doi":"10.3390/pharmaceutics17060796","DOIUrl":"10.3390/pharmaceutics17060796","url":null,"abstract":"<p><p><b>Background/Objective</b>: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with ⁴⁴Sc (t_1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as ⁸⁹Zr (t_1/2 = 78.41 h). <b>Methods</b>: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with ⁴⁴Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (<i>n</i> = 3) for [⁴⁴Sc]Sc-B11-IgG and 73.6 ± 12.1% (<i>n</i> = 3) for [⁴⁴Sc]Sc-B11-nanobody, before purification. <b>Results</b>: Significantly higher uptake in the PD-L1₊ cells than PD-L1_KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. <b>Conclusions</b>: Due to the high non-specific uptake in vitro, the ⁴⁴Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with ⁴⁴Sc, due to their well-matched biological and physical half-life.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLC-Based Rifampicin Delivery System: Development and Characterization for Improved Drug Performance Against <i>Staphylococcus aureus</i>.","authors":"Javiera Carrasco-Rojas, Felipe I Sandoval, Christina M A P Schuh, Carlos F Lagos, Javier O Morales, Francisco Arriagada, Andrea C Ortiz","doi":"10.3390/pharmaceutics17060799","DOIUrl":"10.3390/pharmaceutics17060799","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Rifampicin is a typical antibiotic used for the treatment of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. <b>Methods</b>: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. <b>Results:</b> In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer-Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against <i>S. aureus</i> revealed a substantial increase in potency for NLC-RIF, with an IC₅₀ of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. <b>Conclusions</b>: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of Anaphylaxis Following mRNA-LNP Vaccines: It Is Urgent to Eliminate PEG and Find Alternatives.","authors":"Jinxing Song, Dihan Su, Hongbing Wu, Jeremy Guo","doi":"10.3390/pharmaceutics17060798","DOIUrl":"10.3390/pharmaceutics17060798","url":null,"abstract":"<p><p>The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-Polymer Hybrid Nanoparticles as a Smart Drug Delivery System for Peptide/Protein Delivery.","authors":"Alharith A A Hassan, Eslam Ramadan, Katalin Kristó, Géza Regdon, Tamás Sovány","doi":"10.3390/pharmaceutics17060797","DOIUrl":"10.3390/pharmaceutics17060797","url":null,"abstract":"<p><p>The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic Polymer Micelles as Carriers of Bioactive Sesquiterpene Lactones from <i>Inula Helenium</i> L. for Effective Treatment of Bacterial Biofilms.","authors":"Rumena Stancheva, Tsvetozara Damyanova, Tsvetelina Paunova-Krasteva, Ralitsa Veleva, Tanya Topouzova-Hristova, Viktoria Ivanova, Antoaneta Trendafilova, Ivaylo Dimitrov, Stanislav Rangelov, Emi Haladjova","doi":"10.3390/pharmaceutics17060800","DOIUrl":"10.3390/pharmaceutics17060800","url":null,"abstract":"<p><p><b>Objectives:</b> Nanosized polymeric micelles (PMs) with an average size of about 80 nm and moderately positive ζ potential, based on an amphiphilic poly(4-methyl-piperazin-1-yl)-propenone)-b-polylactide (PMPP-PLA) block copolymer, were prepared. They were used as platforms for the delivery of bioactive sesquiterpene lactones from <i>Inula helenium</i> L. root extract. <b>Methods:</b> The PMs were characterized with good encapsulation efficiency as a maximum value of 72% was reached at a polymer-to-extract mass ratio of 10:1. The loaded micelles exhibited good colloidal stability. An in vitro release was performed showing a burst release profile. The biocompatibility of the resulting PMs was confirmed by assessing their cytotoxic effect on human keratinocytes in vitro by colorimetric assay and flow cytometry. <b>Results</b>: The systems demonstrated the capability to reduce the biomass of pre-formed Gram-positive and Gram-negative bacterial biofilms. <b>Conclusions:</b> The obtained data clearly determine a trend for a strong combined effect between the PMs and the root extract, distinguishing them with an excellent anti-biofilm potential and prospects for future applications in medical practice.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nasal Emulgel's Role in Preventing Coronavirus Infection.","authors":"Francesca Accioni, Giovanna Rassu, Antonio Brunetti, Erika Plicanti, Giulia Freer, Antonio Carta, Paolo Giunchedi, Elisabetta Gavini","doi":"10.3390/pharmaceutics17060795","DOIUrl":"10.3390/pharmaceutics17060795","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Coronaviruses (CoVs) are a large family of respiratory viruses that cause respiratory illnesses ranging from mild colds to severe diseases such as severe acute respiratory syndrome and pandemics. The nasal cavity is a primary site for CoV entry and transmission. The study aimed to prepare a novel mucoadhesive emulgel specifically formulated with simple, safe, and cost-effective excipients to create a barrier on the nasal mucosa that impedes CoV infection. This formulation strategy was specifically designed to enable rapid and straightforward in vivo translation, addressing a critical gap in preventive measures against respiratory viruses. <b>Methods</b>: Three emulgels, containing macadamia oil, Carbopol and different percentages of hydroxypropyl methylcellulose (1, 1.2 and 1.5% (w/v), HPMC), were properly prepared and characterized for mucoadhesion, viscosity, and spreadability. The biological activity against SARS-CoV-2 was evaluated in vitro on infected epithelial cells. <b>Results</b>: The emulgel with 1.2% HPMC demonstrated optimal physicochemical properties (mucoadhesion: 342 ± 9 mN/cm²; viscosity: 1080 ± 83 cp; spreadability: 7.27 ± 0.06 cm) suitable for nasal application. Importantly, in vitro biological assays demonstrated that this emulgel significantly inhibits SARS-CoV-2 infection in epithelial cells, indicating an effective barrier to viral diffusion. <b>Conclusions</b>: By employing readily available, safe, and inexpensive excipients, this novel mucoadhesive emulgel offers a practical, scalable, and rapidly translatable nasal prophylactic approach to prevent early SARS-CoV-2 infection, addressing a critical unmet need in pandemic preparedness.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terpenes and Essential Oils in Pharmaceutics: Applications as Therapeutic Agents and Penetration Enhancers with Advanced Delivery Systems for Improved Stability and Bioavailability.","authors":"Greta Kaspute, Tatjana Ivaskiene, Arunas Ramanavicius, Simonas Ramanavicius, Urte Prentice","doi":"10.3390/pharmaceutics17060793","DOIUrl":"10.3390/pharmaceutics17060793","url":null,"abstract":"<p><p>This review examines the pharmaceutical applications of essential oils (EOs) and terpenes, highlighting their dual role as therapeutic agents and natural penetration enhancers. These volatile, hydrophobic compounds have well-documented antimicrobial, antioxidant, and anti-inflammatory properties. However, their clinical potential is limited by poor water solubility, high volatility, and sensitivity to environmental factors, including light, heat, and oxygen. To address these challenges, various advanced delivery systems have been developed to enhance stability, bioavailability, and controlled release. These systems not only protect chemical integrity but also exploit these compounds' abilities to interact with lipid membranes, facilitating the transport of active compounds across biological barriers. Additionally, their inherent antimicrobial properties can contribute to the overall stability of formulations. The review critically examines the incorporation of terpenes and major essential oil (EO) components, such as limonene, linalool, eugenol, α-pinene, and menthol, into delivery systems, assessing their performance in enhancing drug permeability and targeting specific tissues. Current challenges and future directions in terpenes and EO-based delivery strategies are discussed, highlighting their promising role in developing multifunctional and efficient pharmaceutical formulations.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Laser Sintering of Atomoxetine Tablets: An Innovative Approach for Small-Scale, Personalized Production.","authors":"Gordana Stanojević, Ivana Adamov, Snežana Mugoša, Veselinka Vukićević, Svetlana Ibrić","doi":"10.3390/pharmaceutics17060794","DOIUrl":"10.3390/pharmaceutics17060794","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The growing interest in personalized medicine has accelerated the exploration of three-dimensional (3D) printing technologies in pharmaceutical applications. This study investigates the potential of selective laser sintering (SLS) as a flexible, small-scale manufacturing method for atomoxetine tablets tailored for individualized therapy, comparing it with conventional direct compression. <b>Methods:</b> Atomoxetine tablets were produced using SLS 3D printing with varying laser scanning speeds and compared to tablets made via a compaction simulator. Formulations were based on hydroxypropyl methylcellulose (HPMC) as the primary matrix former. The physical properties, drug content, disintegration time, and dissolution profiles were evaluated. The structural and chemical integrity were assessed using SEM, FTIR, DSC, and XRPD. <b>Results:</b> The SLS tablets exhibited comparable mechanical properties and drug content to those made by compaction. Lower laser speeds produced harder tablets with slower disintegration, while higher speeds yielded more porous tablets with ultra-rapid drug release (>85% in 15 min). All tablets met the European Pharmacopoeia dissolution criteria. No significant drug-excipient interactions or changes in crystallinity were detected. <b>Conclusions:</b> SLS printing is a viable alternative to traditional tablet manufacturing, offering control over drug release profiles through parameter adjustment. The technique supports the development of high-quality, patient-specific dosage forms and shows promise for broader implementation in personalized pharmaceutical therapy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Characterization of Bone-Targeting Vancomycin-Loaded Liposomes.","authors":"Basel Karzoun, Wala'a Albenayan, Shilpa Raut, Eman Atef","doi":"10.3390/pharmaceutics17060792","DOIUrl":"10.3390/pharmaceutics17060792","url":null,"abstract":"<p><p><b>Background:</b> We report the successful formulation of a bone-targeted vancomycin-loaded liposomal carrier. <b>Method:</b> The basic liposomal structure is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dicetyl phosphate (DCP) in a molar ratio of 3:1:0.25, respectively. The dehydration-rehydration method was used to maximize the liposomal-encapsulation efficiency of vancomycin after the initial preparation using thin-film hydration. <b>Results:</b> Sodium alendronate was used as a targeting moiety and was successfully conjugated to DSPE-PEG-COOH via carbodiimide chemistry, as was confirmed using IR spectroscopy. The resulting conjugate, DSPE-PEG-alendronate, was subsequently used in the formulation of bone-targeting vancomycin-loaded liposomes. In vitro binding assays with hydroxyapatite demonstrated preferential binding of the surface-modified liposomes to hydroxyapatite crystals. Furthermore, ex vivo studies revealed that the surface-modified liposomes exhibited enhanced binding affinity to the tibial bone tissue of 4-week-old male CD1 mice, in comparison to unmodified liposomes. <b>Conclusions:</b> The successfully formulated surface-modified vancomycin loaded liposomes showed enhanced bone affinity with a great potential for targeting the antibiotic to infected bones.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Optimization of Grape Skin Extract-Loaded Gelatin-Alginate Hydrogels: Assessment of Antioxidant and Antimicrobial Properties.","authors":"Jovana Bradic, Anica Petrovic, Aleksandar Kocovic, Vukasin Ugrinovic, Suzana Popovic, Andrija Ciric, Zoran Markovic, Edina Avdovic","doi":"10.3390/pharmaceutics17060790","DOIUrl":"10.3390/pharmaceutics17060790","url":null,"abstract":"<p><p><b>Background:</b> In this study, we aimed to develop and optimize unique eco-friendly gelatin-alginate hydrogels enriched with sustainable grape skin extract for advanced wound healing applications. <b>Methods:</b> Following confirmation of the extract's antioxidant activity, hydrogels were synthesized by varying gelatin content and CaCl₂ concentration to achieve desirable crosslinking density, mechanical properties, and extract release behavior. Physicochemical characterization of hydrogels included equilibrium swelling analysis, mechanical testing, FTIR analysis, and in vitro release of extract from hydrogel. Moreover, the biocompatibility of hydrogels enriched with extract was assessed via MTT assay, while antimicrobial activity was tested against <i>Staphylococcus aureus</i> ATCC 25923, <i>Escherichia coli</i> ATCC 25922, <i>Pseudomonas aeruginosa</i> ATCC 10145, and <i>Candida albicans</i> ATCC 10231. The antioxidant capacity of the hydrogels was evaluated using DPPH, ABTS, and FRAP assays. <b>Results:</b> Our results showed that higher gelatin and CaCl₂ concentrations produced denser crosslinked networks, leading to reduced swelling and increased stiffness. Additionally, the extract exhibited a biphasic release profile from hydrogels, featuring an initial rapid release followed by sustained release over 24 h. <b>Conclusions:</b> The hydrogels maintained high biocompatibility and demonstrated selective antimicrobial activity, particularly against <i>Escherichia coli</i>, and satisfactory antioxidant activity. Obtained multifunctional sustainable hydrogels enriched with grape skin extract represent promising agents for managing skin conditions associated with oxidative stress and bacterial infections.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}