Pharmaceutics最新文献

{"title":"Identification of Variable Lymphocyte Receptors That Target the Human Blood-Brain Barrier.","authors":"Moriah E Katt, Elizabeth A Waters, Benjamin D Gastfriend, Brantley R Herrin, Max D Cooper, Eric V Shusta","doi":"10.3390/pharmaceutics17091179","DOIUrl":"10.3390/pharmaceutics17091179","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Receptor-mediated transcytosis utilizing the native transporters at the blood-brain barrier (BBB) is a growing strategy for the delivery of therapeutics to the brain. One of the major challenges in identifying appropriate human transcytosis targets is that there is a species-specific transporter expression profile at the BBB, complicating translation of successful preclinical candidates into humans. In an effort to overcome this obstacle and identify proteins capable of binding human-relevant BBB ligands, we generated and screened a BBB-targeting library against human-induced pluripotent stem cell-derived brain microvascular endothelial-like cells (iPSC-derived BMEC-like cells). As targeting molecules, we used lamprey antibodies, known as variable lymphocyte receptors (VLRs), and generated a VLR library by immunizing lamprey with iPSC-derived BMEC-like cells, and inserting the resultant VLR repertoire into the yeast surface display system. <b>Methods</b>: The yeast displayed VLR library was then panned against human iPSC-derived BMEC-like cells and lead VLRs were validated using human in vitro models and mouse and human ex vivo brain tissue sections. <b>Results</b>: Finally, brain uptake for a set of VLRs was validated in mice. Of the 15 lead VLR candidates, 14 bound to human BBB antigens, and 10 bound to the murine BBB. Pharmacodynamic testing using the neuroactive peptide neurotensin indicated that the lead candidate, VLR2G, could cross the mouse BBB after intravenous injection and deliver sufficient neurotensin payload to generate a pharmacological response and lower systemic body temperature. <b>Conclusions</b>: Together, these results demonstrate the application of a novel screening technique capable of identifying a VLR with human relevance that can cross the BBB and deliver a payload.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177313","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":"3D Bioprinted Neural Tissues: Emerging Strategies for Regeneration and Disease Modeling.","authors":"Taekyung Choi, Jinseok Park, Suvin Lee, Hee-Jae Jeon, Byeong Hee Kim, Hyun-Ouk Kim, Hyungseok Lee","doi":"10.3390/pharmaceutics17091176","DOIUrl":"10.3390/pharmaceutics17091176","url":null,"abstract":"<p><p>Three-dimensional (3D) bioprinting has emerged as a versatile platform in regenerative medicine, capable of replicating the structural and functional intricacies of the central and peripheral nervous systems (CNS and PNS). Beyond structural repair, it enables the construction of engineered tissues that closely recapitulate neural microenvironments. This review provides a comprehensive and critical synthesis of current bioprinting strategies for neural tissue engineering, with particular emphasis on comparing natural, synthetic, and hybrid polymer-based bioinks from mechanistic and translational perspectives. Distinctively, it highlights gradient-based modulation of Schwann cell behavior and axonal pathfinding using mechanically and chemically patterned constructs. Special attention is given to printing modalities such as extrusion, inkjet, and electrohydrodynamic jet printing, examining their respective capacities for controlling spatial organization and microenvironmental cues. Representative applications include brain development models, neurodegenerative disease platforms, and glioblastoma scaffolds with integrated functional properties. Furthermore, this review identifies key translational barriers-including host tissue integration and bioink standardization-and explores emerging directions such as artificial intelligence-guided biofabrication and organ-on-chip integration, to enhance the fidelity and therapeutic potential of neural bioprinted constructs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177336","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":"Integrating Microorganism-Based Therapy and Emerging Biotechnology in the Treatment of Intracranial Central Nervous System Diseases.","authors":"Zifan Li, Shihua Yang, Lida Su","doi":"10.3390/pharmaceutics17091175","DOIUrl":"10.3390/pharmaceutics17091175","url":null,"abstract":"<p><p>The development of drug delivery systems for the treatment of intracranial central nervous system (CNS) diseases remains one of the most intractable medical problems in modern society, owing to the special physiological structure of the brain, including the existence of the blood-brain barrier (BBB), the CNS's immune privilege, and its high complexity and vulnerability. Recently, a leading approach in the CNS drug delivery domain has been to employ or simulate the physiological behavior of microorganisms to overcome the BBB and remodel the pathological immune microenvironment in intracranial tissue. Considering the exceptional advancements in microorganism-based CNS drug delivery systems, it is imperative to review the latest breakthroughs. Herein, we summarize the emerging trends at the intersection of microorganism-based drug delivery systems and emerging biomedical technology for the treatment of CNS diseases, with a particular focus on preclinical research into microorganism-based drug delivery systems to combat CNS diseases, aiming to describe a credible landscape for further clinical trials.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177403","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":"<i>Etrog Citron</i> (<i>Citrus medica</i>) as a Novel Source of Antiviral Agents: Overview of Its Bioactive Phytochemicals and Delivery Approaches.","authors":"Arik Dahan, Ludmila Yarmolinsky, Faina Nakonechny, Olga Semenova, Boris Khalfin, Sigal Fleisher-Berkovich, Shimon Ben-Shabat","doi":"10.3390/pharmaceutics17091173","DOIUrl":"10.3390/pharmaceutics17091173","url":null,"abstract":"<p><p>The recent COVID-19 pandemic highlighted the significant challenge of insufficient antiviral pharmacological options. Edible plants offer a promising avenue for developing novel antiviral drugs. Etrog citron (<i>Citrus medica</i> L.), which is a valuable edible and medicinal plant, contains various antiviral phytochemicals, mainly flavonoids, coumarins, and terpenes. However, the therapeutic application of these compounds remains limited by factors such as poor solubility, limited bioavailability, and unclear mechanisms of action. The aim of the present article is to offer a comprehensive analysis of the antiviral phytochemicals extracted from various parts of <i>Citrus medica</i>, emphasizing their mode of action and delivery strategies that may allow turning these compounds into new antiviral drugs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177357","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":"Modeling and Design of Chitosan-PCL Bi-Layered Microspheres for Intravitreal Controlled Release.","authors":"Eduardo A Chacin Ruiz, Samantha L Carpenter, Katelyn E Swindle-Reilly, Ashlee N Ford Versypt","doi":"10.3390/pharmaceutics17091174","DOIUrl":"10.3390/pharmaceutics17091174","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Chronic retinal diseases usually require repetitive local dosing. Depending on factors such as dosing frequency, mode of administration, and associated costs, this can result in poor patient compliance. A better alternative involves using controlled-release drug delivery systems to reduce the frequency of intravitreal dosing and extend drug release. However, reaching the market stage is a time-consuming process. <b>Methods:</b> In this study, we employed two computational approaches to model and estimate the parameters governing the diffusion-controlled drug release from bi-layered microspheres. The case study involved microspheres composed of a chitosan core and a polycaprolactone (PCL) shell. The model drugs were bovine serum albumin and bevacizumab (an agent that slows neovascularization due to retinal disorders). Drug release from the microspheres is described by a mathematical model that was solved numerically using the finite difference and the finite element approaches. The parameter estimation was performed by nonlinear least-squares regression. <b>Results:</b> We used the estimated parameters to simulate the cumulative release under various conditions and optimize the device design to guide future experimental efforts and improve the duration of release beyond a target daily therapeutic release rate from the microspheres. <b>Conclusions:</b> We investigated the effects of polymeric layer sizes on drug release and provided recommendations for optimal sizes. We provide straightforward computational tools for others to reuse in designing bi-layered microspheres for intravitreal drug delivery needs in the treatment of chronic ocular neovascularization.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177511","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":"Electrospun PMVEMA Nanofibers Developed as a Fast-Release Platform for Antineoplastic Drugs Tested in Glioblastoma Primary Cultures.","authors":"Pedro Valentín Badía-Hernández, Joan Moll Carrió, María Fuentes-Baile, María Losada-Echeberría, Rocío Díaz-Puertas, Amalia Mira, Miguel Saceda, Pilar García-Morales, Ricardo Mallavia","doi":"10.3390/pharmaceutics17091172","DOIUrl":"10.3390/pharmaceutics17091172","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The local release of antineoplastic drugs in post-surgical treatments is an alternative way to improve their effectiveness against glioblastoma reappearance. Thus, it was proposed to develop a local delivery system based on electrospun PMVEMA-derived nanofibers for the administration of carmustine (BCNU), temozolomide (TMZ), and doxorubicin (DOX). <b>Methods</b>: Electrospun nanofibers were prepared using PMVEMA-monoethyl ester (PMVEMA-Es) and PMVEMA-acid (PMVEMA-Ac), loading BCNU, TMZ, and DOX at 1% or 8% (<i>w</i>/<i>w</i>). Their morphology, encapsulation efficiency, and release profiles were characterized by FESEM, confocal microscopy, and HPLC. Their biological effects were evaluated through cell viability, cell cycle, and intracellular accumulation assays in established cell lines from glioblastoma patients (HGUE-GB) and human astrocytes (HAs). <b>Results</b>: The nanofibers were optimized without defects, and encapsulation efficiencies were above 80%. The release studies showed a rapid initial release in the first hour, being DOX > TMZ > BCNU, while the second release rate was sustained in the cases of PMVEMA-Ac/TMZ (0.14%/h) and PMVEMA-Es/BCNU (1.2%/h), highlighting that, after 24 h under physiological conditions, the degradation of the loaded drug was lower than its free state, comparable to the Gliadel release system. Furthermore, it was confirmed that there was a dose-dependent decrease in cell viability for PMVEMA-Es/BCNU and PMVEMA-Ac/DOX, with higher cytotoxicity than free DOX. Finally, the lowest concentration tested had a relatively low effect on HAs compared with its effect on glioblastoma cells. <b>Conclusion</b>: PMVEMA-based electrospun nanofibers are effective in encapsulating and releasing antineoplastic drugs, suggesting their potential as a local delivery system to improve glioblastoma post-surgical treatment efficacy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177430","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":"The Preservation of the Therapeutic Efficacy of the Secretome of Adipose Mesenchymal Stem Cells, Produced in the Presence of Antioxidant and Anti-Inflammatory Drugs.","authors":"Sofia Martinez-Rodriguez, Nahla Jemni-Damer, Atocha Guedan-Duran, Girish K Srivastava, Fivos Panetsos","doi":"10.3390/pharmaceutics17091171","DOIUrl":"10.3390/pharmaceutics17091171","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Inflammatory processes, both acute and chronic, encompass a wide range of autoimmune, metabolic, and neurodegenerative conditions. Conventional treatments, primarily anti-inflammatories and immunosuppressants, provide partial relief but are often hampered by adverse effects and limited durability. Mesenchymal stem cells (MSCs) have emerged as a powerful new treatment due to their immunomodulatory and anti-inflammatory properties, primarily mediated through their secretome, which is a complex mixture of bioactive factors. Secretome-based therapeutic strategies show strong potential for controlling inflammation, mitigating oxidative stress, and supporting tissue regeneration and repair. However, the therapeutic efficacy of MSCs' secretome is subject to modification by concurrent anti-inflammatory drug regimens used in clinical settings. <b>Methods:</b> To evaluate the effect of combinatorial treatment strategies on the secretome of the MSCs, we employed an in vitro retinal inflammation model to investigate whether the exposure of the MSCs to five representative anti-inflammatory drugs (ketorolac, diclofenac, α-lipoic acid, N-acetyl-L-cysteine, and nicotinamide) impacts the functionality of the resulting secretome. Specifically, we evaluated the effect of the above-mentioned drugs on the anti-inflammatory properties of the secretome in relation to the secreted levels of two main MSC secretome factors-the Brain-Derived Neurotrophic Factor (BDNF) and the Vascular Endothelial Growth Factor (VEGF)-and on the secretome's pro-metabolic activity. <b>Results:</b> Our findings provide evidence that the presence of any of the tested drugs during MSC secretome production does not compromise its anti-inflammatory activity; BDNF and VEGF levels remain stable, and the secretome retains a high degree of its pro-metabolic effect. <b>Conclusions:</b> These results underscore the robustness and clinical resilience of MSC-based therapies, even when administered alongside pharmacological agents. This work advances the translational viability of MSC therapies for inflammatory diseases and supports the development of safe, combinatorial treatment strategies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177280","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":"In Vitro Antifungal Activity of Amphotericin B-Encapsulated Silk Fibroin-Chitosan Nanoparticles Against <i>Fusarium solani</i> Isolates from Keratitis Patients.","authors":"Rossukon Khotcharrat, Sangly P Srinivas, Yordhathai Thongsri, Wanachat Thongsuk","doi":"10.3390/pharmaceutics17091170","DOIUrl":"10.3390/pharmaceutics17091170","url":null,"abstract":"<p><p><b>Background:</b> Fungal keratitis is a serious ophthalmic problem due to low antifungal medication penetration and bioavailability at the ocular surface, necessitating novel delivery strategies for successful therapeutic outcomes. This study created amphotericin B-loaded silk fibroin nanoparticles (AmB-SFNs) as a targeted drug delivery platform for long-term ocular antifungal therapy. <b>Methods</b>: Silk fibroin-chitosan nanoparticles were produced using a precipitation technique, with chitosan coating for mucoadhesion and polyethylene glycol-400 surface stability. Clinical fungal isolates from keratitis patients were identified as species by morphological and molecular analysis, followed by in vitro antifungal susceptibility testing. <b>Results</b>: The optimized formulation produced spherical AmB-SFNs with an average diameter of 220 nm, a positive zeta potential of +34 mV, and a maximum amphotericin B entrapment effectiveness of 76%. Molecular identification confirmed that all five clinical isolates were <i>Fusarium solani</i>. AmB-SFNs showed strong antifungal activity against all tested isolates, with a minimum inhibitory dose of 50 μg/mL (0.25% <i>w</i>/<i>v</i>). <b>Conclusions</b>: The developed nanoparticulate system has optimal characteristics for enhanced corneal drug delivery, such as appropriate particle size for tissue penetration and mucoadhesive properties for prolonged ocular residence time, suggesting that this nanoparticulate system warrants further investigation in vivo to evaluate its potential for clinical translation in treating Fusarium keratitis and as a platform for topical ophthalmic therapies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177281","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":"Cracking the Blood-Brain Barrier Code: Rational Nanomaterial Design for Next-Generation Neurological Therapies.","authors":"Lucio Nájera-Maldonado, Mariana Parra-González, Esperanza Peralta-Cuevas, Ashley J Gutierrez-Onofre, Igor Garcia-Atutxa, Francisca Villanueva-Flores","doi":"10.3390/pharmaceutics17091169","DOIUrl":"10.3390/pharmaceutics17091169","url":null,"abstract":"<p><p>This review provides a mechanistic framework to strategically design nanoparticles capable of efficiently crossing the blood-brain barrier (BBB), a critical limitation in neurological treatments. We systematically analyze nanoparticle-BBB transport mechanisms, including receptor-mediated transcytosis, adsorptive-mediated transcytosis, and transient barrier modulation. Essential nanoparticle parameters (size, shape, stiffness, surface charge, and biofunctionalization) are evaluated for their role in enhancing brain targeting. For instance, receptor-targeted nanoparticles can significantly enhance brain uptake, achieving levels of up to 17.2% injected dose per gram (ID/g) in preclinical glioma models. Additionally, validated preclinical models (human-derived in vitro systems, rodents, and non-human primates) and advanced imaging techniques crucial for assessing nanoparticle performance are discussed. Distinct from prior BBB nanocarrier reviews that primarily catalogue mechanisms, this work (i) derives quantitative 'design windows' (size 10-100 nm, aspect ratio ~2-5, near-neutral ζ) linked to transcytosis efficiency, (ii) cross-walks human-relevant in vitro/in vivo models (including TEER thresholds and NHP evidence) into a translational decision guide, and (iii) integrates regulatory/toxicology readiness (ISO 10993-4, FDA/EMA, ICH) into practical checklists. We also curate recent (2020-2025) %ID/g brain-uptake data across lipidic, polymeric, protein, inorganic, and hybrid vectors to provide actionable, evidence-based rules for BBB design.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177328","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 of 3D-Printed Gel-Based Supplement-Containing Tablets with Tailored Release Profiles for Neurological Pain Management.","authors":"Jurga Andreja Kazlauskaite, Inga Matulyte, Jurga Bernatoniene","doi":"10.3390/pharmaceutics17091168","DOIUrl":"10.3390/pharmaceutics17091168","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Neuropathic pain, resulting from damage or pathology affecting the somatosensory nervous system, is a prevalent form of chronic pain that significantly impacts quality of life. Combined therapies are often utilised to manage this condition. Three-dimensional printing (3DP) offers a promising approach for personalising medication doses and dosage forms to meet individual patient needs. <b>Methods</b>: In this study, a formulation suitable for 3D printing was developed using magnesium citrate, uridine monophosphate, vitamins B₃ (niacin), B₆ (pyridoxine), B₁₂ (cobalamin), B₉ (folic acid), and spermidine to create a novel gel-based oral tablet for the targeted treatment of neurological pain. The antioxidant potential of the active pharmaceutical ingredients (APIs) was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods. The physical properties of the tablets were evaluated using a texture analyser, while the in vitro release profiles were determined by high-performance liquid chromatography (HPLC). <b>Results</b>: Results demonstrated that pectin-gelatin tablets hardened over time, with higher citric acid concentrations further enhancing this effect. Formulation AVII exhibited good hardness and low stickiness. Formulation AV, however, showed poor performance across all physical parameters and lacked sufficient structural integrity for practical application. While uridine monophosphate, B₁₂, and B₉ showed no significant differences in the release profiles of the tablets, spermidine, B₆, and B₃ displayed statistically significant variations. Specifically, AVII outperformed AV in terms of spermidine and B₆ release, and AV showed a higher release of B₃ compared to AV. <b>Conclusions</b>: The AVII tablet demonstrates potential for use in combined therapy targeting neurological pain disorders.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177345","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}