AAPS PharmSciTech最新文献

{"title":"Innovative Drug Development Approach to Address the Transition to Low Global Warming Potential Propellant Using Hydrofluoroalkane-152a, for Triple Combination Pressurized Metered-Dose Inhaler Products Targeting Small Airways","authors":"A. Matturro,&nbsp;E. Zambelli,&nbsp;E. Cuoghi,&nbsp;D. Copelli,&nbsp;F. Usberti,&nbsp;A. Fioni,&nbsp;L. Labadini","doi":"10.1208/s12249-025-03057-z","DOIUrl":"10.1208/s12249-025-03057-z","url":null,"abstract":"<div><p>Recent and emerging environmental policies have boosted the investigation of pressurized metered-dose inhalers (pMDI) that have a minimal impact on climate change. There is a current move away from existing hydrofluorocarbon (HFC)-based propellants, specifically the hydrofluoroalkane (HFA)-134a and HFA-227ea based pMDI products that are approved for the treatment of asthma and chronic obstructive pulmonary disease (COPD), towards those that use low global warming potential (LGWP) propellants. Changing the propellant to, for example, the less environmentally-damaging HFA-152a, is a focus for many manufacturers. In this paper, we report an innovative approach to developing new pMDI drug products with a LGWP propellant. Moreover, proof of the hypothesis that products containing the current propellant and those using a LGWP propellant can achieve equivalent performance is reported, by showing comparability of a triple combination pMDI (Trimbow®) formulated using the LGWP HFA-152a propellant compared with HFA-134a. This paper will present the use of <i>in silico</i> mathematical modelling, leveraging on Chiesi proprietary Modulite® principles to predict and validate <i>in vitro</i> performances of the drug product under development. Validation is carried out using realistic aerodynamic particle size distribution (rAPSD), a novel approach that offers a more accurate prediction of aerosol distribution by incorporating variations compared to the standard aerodynamic particle size distribution (APSD). Additional <i>in vitro</i> testing validates the prediction of <i>in silico</i> models and confirms good comparability in terms of aerodynamic performance between HFA-152a and HFA-134a, which translates <i>in vivo</i> as evidenced by the preliminary pharmacokinetics (PK) in animal models and the formal clinical PK bioequivalence (BE) studies. (Rony et al. in Pulm Pharmacol Ther 85, 2024).</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03057-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Uptake and Trafficking of Lipid Nanocarriers Using High-Resolution Electron Microscopy","authors":"Thilo Faber,&nbsp;Alf Lamprecht","doi":"10.1208/s12249-025-03061-3","DOIUrl":"10.1208/s12249-025-03061-3","url":null,"abstract":"<div><p>Lipid based nanocarriers are a commonly used drug delivery system with cargos ranging from small molecules to complex RNA-based therapies. There are several hypotheses how such carriers can enter the cell, in which organelles they reside, and how they cross or escape the endo-lysosomal system. To provide additional insights, the cell-nanocarrier interplay was visualized exemplarily with lipid-based nanocarriers and macrophage-like cultured cells (J774A.1 cells) using high resolution electron microscopy. Nanocarrier uptake into J774A.1 cells was detectable after the first 15 min by intracellular accumulation of electron-dense material. These accumulations were identified as lysosomes and lipid droplets, indicating complete degradation and a subsequent formation of storage organelles as early as 15 min. Inhibition of lysosomal acid lipase did not block lipid droplet formation, but rather resulted in accumulation of lipid droplets within lysosomes. This suggests that other cellular lipases already degrade acylglycerols before they reach lysosomes. Chloroquine co-treatment allowed visualization of nanocarriers inside endosomal vesicles, multivesicular bodies, and lysosomes.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03061-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrospinning: A New Frontier in Peptide Therapeutics","authors":"Jeyanthi L.,&nbsp;Sivadharshini Kamaraj,&nbsp;Ruckmani Kandasamy,&nbsp;Shanmugarathinam Alagarsamy","doi":"10.1208/s12249-025-03054-2","DOIUrl":"10.1208/s12249-025-03054-2","url":null,"abstract":"<div><p>The nanofiber technology has recently undergone an unprecedented transformation, finding widespread utilities across diverse scientific disciplines. It is noteworthy that electrospinning approaches have emerged as an adaptable and successful approach to generate fibers ranging in rapidly as a class of therapeutic agents with a high level of target specificity. Peptides encounter several challenges as drugs, including swift breakdown by the body, rapid elimination from the bloodstream, inadequate stability, and restricted ability to cross cell membranes. This renders it challenging to employ them as drugs. However, electrospun nanofibers might address these problems. This review explores the promising potential of electrospinning nanofibers for peptide delivery. We delve into recent advancements in this technique, highlighting its effectiveness in overcoming challenges associated with peptide drug delivery. It provides an analysis of the trends identified in the use of the electrospinning technique and its role in peptide drug delivery systems, based on a review of data collected over a period of five to seven years.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microemulsions Improve the Cutaneous Co-Localization of Lipoic Acid and Quercetin and Antioxidant Effects in Cutaneous Cells and Tissue","authors":"Mariana de Sousa Silva,&nbsp;Julia S. Passos,&nbsp;Regina G. Daré,&nbsp;Jessica R. Nunes,&nbsp;Patricia P. Adriani,&nbsp;Luciana B. Lopes","doi":"10.1208/s12249-025-03062-2","DOIUrl":"10.1208/s12249-025-03062-2","url":null,"abstract":"<div><p>Quercetin and α-lipoic acid are antioxidants with potential applications in the treatment of various skin conditions, such as wounds and chemoprevention of skin cancer. To enable their effective topical co-delivery and co-localization in the tissue, we developed microemulsions (ME). The selected ME (ME-50) formed a stable system with a mean droplet size of 134.4 ± 17.9 nm, increasing to 224.9 ± 19.9 nm upon antioxidants co-incorporation. The ME preserved the antioxidant capacities of the molecules, with DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay showing an IC₅₀ of 6.2 ± 0.1 µg/mL, similar to the solution. Skin penetration studies revealed a 2.4-fold increase in quercetin (Q) accumulation in the stratum corneum and a 3.5-fold increase in the delivery to viable epidermis and dermis (ED) after a 12 h-treatment with the ME compared to control solutions; α-lipoic acid (LA) penetration improved up to 1.9-fold in ED upon ME incorporation. Treatment with Q + LA co-loaded ME enhanced the antioxidant activity in the stratum corneum and ED by 1.3-fold and 2.0-fold, respectively, compared to solutions. Treatment with the ME for 24 h also reduced oxidative species levels by 55% in H₂O₂-exposed keratinocytes compared to the control (untreated) cells. Taken together, these results suggest that ME-50 is a promising delivery system for enhancing the cutaneous co-delivery of quercetin and α-lipoic acid and the antioxidant effects in the tissue, offering a potential topical treatment for oxidative stress-related skin conditions.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic Nanoparticle Based Targeted mRNA Vaccine Delivery as a Novel Therapy for Glioblastoma Multiforme","authors":"Tanvir Ahmed,&nbsp;Kazi Tasnuva Alam","doi":"10.1208/s12249-025-03065-z","DOIUrl":"10.1208/s12249-025-03065-z","url":null,"abstract":"<div><p>The prognosis for patients with glioblastoma multiforme (GBM), an aggressive and deadly brain tumor, is poor due to the limited therapeutic options available. Biomimetic nanoparticles have emerged as a promising vehicle for targeted mRNA vaccine delivery, thanks to recent advances in nanotechnology. This presents a novel treatment method for GBM. This review explores the potential of using biomimetic nanoparticles to improve the specificity and effectiveness of mRNA vaccine against GBM. These nanoparticles can evade immune detection, cross the blood–brain barrier, &amp; deliver mRNA directly to glioma cells by mimicking natural biological structures. This allows glioma cells to produce tumor-specific antigens that trigger strong immune responses against the tumor. This review discusses biomimetic nanoparticle design strategies, which are critical for optimizing transport and ensuring targeted action. These tactics include surface functionalization and encapsulation techniques. It also highlights the ongoing preclinical research and clinical trials that demonstrate the therapeutic advantages and challenges of this strategy. Biomimetic nanoparticles for mRNA vaccine delivery represent a new frontier in GBM treatment, which could impact the management of this deadly disease and improve patient outcomes by integrating cutting-edge nanotechnology with immunotherapy.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral pH-Sensitive Solid Self-Microemulsion of Norcantharidin Wrapped in Colon-Coated Capsule for Selective Therapy of Colorectal Carcinoma","authors":"Xia Liu,&nbsp;Wenyou Fang,&nbsp;Wenjie Lu,&nbsp;Mingchao Xu,&nbsp;Zijun Wu,&nbsp;Dan Su,&nbsp;Lingzhen Ding,&nbsp;Qing Zhang,&nbsp;Jinguang Ouyang,&nbsp;Tianming Wang,&nbsp;Lingfeng Sun,&nbsp;Song Gao,&nbsp;Hui Cheng,&nbsp;Rongfeng Hu","doi":"10.1208/s12249-025-03056-0","DOIUrl":"10.1208/s12249-025-03056-0","url":null,"abstract":"<div><p>Due to the poor solubility, permeability, stability and tumor-targeting ability of norcantharidin (NCTD), currently commercially available NCTD formulations require patients to take the medicine more frequently. Moreover, the formulation of NCTD themselves have certain toxicity, thus showing unsatisfactory therapeutic outcomes and serious systemic side effects. Based on the specific acidic environment at the tumor site, in this study, the pH-sensitive NCTD solid self-microemulsion (NCTD@CS-DMMA SSME) was prepared by introducing 2,3-dimethylmaleic acid amide modified chitosan (CS-DMMA), and it was wrapped in colon-coated capsule to achieve stable and controlled drug release in the acidic environment of colonic tumors. After self-emulsification, it had a particle size of 75.88 ± 0.85 nm and carried a negative charge. Under the condition of pH 6.5, NCTD@CS-DMMA SSME exhibited first-order release kinetics characteristics. Moreover, the cumulative release under the condition of pH 6.5 was 2.04-fold higher than that under the condition of pH 7.4. The <i>in situ</i> intestinal absorption assay elucidated that the prepared formulation could effectively improve the absorption rate constant and apparent permeability coefficients of NCTD in colon tumor site. The antitumor effect <i>in vivo</i> and <i>in vitro</i> showed that it could not only improve the inhibition ability of tumor growth, migration and invasion in mice, but also increase the tumor-infiltrating T lymphocytes in mice with colon cancer, thus inhibiting tumor growth. In summary, the NCTD@CS-DMMA SSME can deliver drugs to the site of colon tumors and continuously release drugs, providing new insights into improving the treatment effectiveness of colon cancer.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocrystals for Intravenous Drug Delivery: Composition Development, Preparation Methods and Applications in Oncology","authors":"Wanjiao Chen,&nbsp;Jingyi Huang,&nbsp;Yankun Guo,&nbsp;Xinyv Wang,&nbsp;Zhizhe Lin,&nbsp;Ruting Wei,&nbsp;Jianming Chen,&nbsp;Xin Wu","doi":"10.1208/s12249-025-03064-0","DOIUrl":"10.1208/s12249-025-03064-0","url":null,"abstract":"<div><p>Intravenous routes of drug delivery are widely used in clinical practice due to the advantages of fast onset of action and avoidance of first-pass effect. Still, it is difficult to develop poorly water-soluble drugs for intravenous administration. In recent years, the application of nanocrystal technology has become more and more widespread, mainly involving reducing the particle size to the nanoparticle size range and improving its physicochemical properties to enhance the bioavailability of drugs. Intravenous nanocrystals (INCs) can show unique advantages in the vasculature, with their high drug loading capacity, low toxicity, and overcoming low solubility, which makes them a new solution in tumor therapy. In addition, INCs are mainly suspended in aqueous/oil phase media, which makes them easy to inject. Therefore, INCs may serve as a novel strategy to address poor water solubility, low bioavailability, and associated toxicity. This review contains the compositional development of INCs, and preparation methods, and provides some insights into their application in oncology.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hansen Solubility Parameters, Computational, and Thermodynamic Models for Tofacitinib Citrate Solubility in Neat Mono Solvents, and GastroPlus Based Predicted In Vivo Performance of Subcutaneous Solution in Humans","authors":"Iman Ehsan,&nbsp;Mudassar Shahid,&nbsp;Subramanian Natesan,&nbsp;Abdul Faruk,&nbsp;Ashwani Kumar Sood,&nbsp;Tasneem Khan","doi":"10.1208/s12249-025-03048-0","DOIUrl":"10.1208/s12249-025-03048-0","url":null,"abstract":"<div><p>We investigated the experimental solubility of tofacitinib citrate (TNF) in HSPiP predicted mono solvents at varied temperature points, followed by validation with various models (computational and thermodynamic) and GastroPlus based predicted <i>in-vivo</i> performance in individuals (adult humans). HSPiP (Hansen software) predicted five mono solvents (N-methyl-2-pyrrolidone as NMP, ethanol, polyethylene glycol 400 as PEG400, chloroform, and water). The thermally stable drug was solubilized in these solvents. Computational (Van't Hoff and Apelblat) models were applied to validate the experimental solubility data (mole fraction solubility, X_e). The selected solvent (NMP) was used as a vehicle for subcutaneous (sub-Q) formulation development and compared against conventional tablet for high effectiveness in terms of pharmacokinetic parameters (PK) in humans. Results showed that the drug solubility in NMP was “endothermic and entropy” driven as evidenced with the applied models (computational and thermodynamic). The optimized components for sub-Q delivery were NMP (21.5% v/v), PEG400 (10.0% v/v), and PBS (phosphate buffer solution at pH 7.4). GastroPlus predicted 0.036 µg/mL and 0.042 µg/mL values of C_max (maximum drug reached in the blood) in the blood after sub-Q and oral delivery, respectively. <i>In vivo</i> access of the drug was maximally extended in sub-Q delivery as compared to tablets as predicted in GastroPlus considering humans (fast condition). Conclusively, the sub-Q administration of TNF can be a promising alternative to the conventional tablets.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Materials Compatibility Considerations for the Transition to Low Global Warming Potential Propellants for Pressurized Metered Dose Inhalers","authors":"Dan Dohmeier,&nbsp;Atish Sen,&nbsp;Alessandro Cavecchi,&nbsp;João Matos,&nbsp;Richard Lostritto,&nbsp;Lee Nagao","doi":"10.1208/s12249-025-03060-4","DOIUrl":"10.1208/s12249-025-03060-4","url":null,"abstract":"<div><p>Pressurized metered dose inhalers (pMDI) are a vital therapy for the treatment of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). In pMDI, the propellants used to deliver the drug to the lungs are hydrofluorocarbons (HFC). However, the current HFCs in use have large global warming potential (GWP). In order to reduce or eliminate the use of propellants with large global warming potential, efforts are underway within the pharmaceutical industry to transition to the use of low GWP propellants in pMDI, while maintaining their effectiveness in treating disease. The current switch from higher GWP propellants mirrors the switch from chlorofluorocarbon (CFC) propellants to HFCs undertaken in the 1990’s, which was driven by ozone depletion concerns. In this paper, the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) discusses aspects of the switch to low GWP propellants from the perspective of materials compatibility of pMDI components with low GWP propellants. Leveraging the learnings and advances in pMDI component materials implemented following the switch from CFCs, industry is well positioned to make the change. This paper describes the utility of the low GWP propellants being developed for use in pMDI and the learnings from the previous transition that are being leveraged by industry. The current state of development will be described, including a review of available literature supporting the transition to low GWP propellants.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03060-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Mucoadhesive Vaginal Films for Metronidazole Delivery Using Methacryloylated, Crotonoylated, and Itaconoylated Gelatin Blends with Poly(vinyl alcohol)","authors":"Elvira O. Shatabayeva,&nbsp;Daulet B. Kaldybekov,&nbsp;Zarina A. Kenessova,&nbsp;Rysgul N. Tuleyeva,&nbsp;Sarkyt E. Kudaibergenov,&nbsp;Vitaliy V. Khutoryanskiy","doi":"10.1208/s12249-025-03055-1","DOIUrl":"10.1208/s12249-025-03055-1","url":null,"abstract":"<div><h3>Purpose</h3><p>This work reports the development and characterisation of polymeric films composed of gelatin or its chemically modified derivatives (crotonoylated, itaconoylated, and methacryloylated gelatins) blended with polyvinyl alcohol (PVA). Metronidazole served as an antimicrobial drug in these formulations.</p><h3>Methods</h3><p>The films were produced by casting aqueous solutions of polymers, followed by solvent evaporation. Their structure and physicochemical characteristics were studied using Fourier transform infrared spectroscopy, scanning electron microscopy, and mechanical testing. The thickness of the films, their folding endurance, the surface pH, and transparency were also evaluated. The mucoadhesive performance of the films was evaluated through an <i>ex vivo</i> detachment technique involving freshly excised sheep vaginal tissues. <i>In vitro</i> cumulative drug release studies were conducted using Franz diffusion cells.</p><h3>Results</h3><p>The results demonstrate that incorporating unsaturated functional groups into gelatin improves its mucoadhesive properties compared to native gelatin. The drug release experiments conducted <i>in vitro</i> showed that the cumulative release from pure gelatin/PVA films was found to be 49 ± 2%, whereas modified gelatins/PVA (70:30) films released ~ 64–71%.</p><h3>Conclusion</h3><p>These findings suggest that modified gelatins could serve as effective excipients in designing mucoadhesive formulations for vaginal administration, with potential applications extending to other transmucosal drug delivery systems.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03055-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}