Pharmaceutics最新文献

{"title":"Studying Peripheral Neuropathy and Associated Neuropathic Pain in HIV-1 Transgenic Rats: Evaluation of the Therapeutic Effect of Cannabidiol and Beta-Caryophyllene.","authors":"Mohammed Alnoud, Jose Rios, Salique H Shaham, Manish K Tripathi, Khalid Benamar","doi":"10.3390/pharmaceutics18091176","DOIUrl":"10.3390/pharmaceutics18091176","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Peripheral neuropathy affects up to 50% of people living with HIV (PLWH). Currently, no small translational rodent model accurately replicates the peripheral neuropathy observed in PLWH. The primary objectives of this study are to assess whether HIV transgenic (HIV-tg) rats develop peripheral neuropathy with pathological and pain-like behaviors similar to those observed in PLWH and to evaluate the analgesic effects of the non-psychoactive cannabis compounds cannabidiol (CBD) and β-caryophyllene (BCP) in HIV-related neuropathic pain. <b>Methods</b>: We used a comprehensive set of behavioral, pharmacological, molecular, biochemical, and proteomic approaches. <b>Results</b>: Tissue analyses showed that HIV-tg rats had significantly reduced intra-epidermal nerve fiber density and increased macrophage infiltration in the dorsal root ganglion compared with control wild-type rats. Behavioral assessments demonstrated that HIV-tg rats developed mechanical allodynia and ongoing pain. β-caryophyllene (BCP) demonstrated higher efficacy than cannabidiol (CBD) in alleviating HIV-related neuropathic pain. Proteomic analysis identified specific proteins uniquely modulated by the analgesic effects of BCP compared to vehicle in HIV-tg rats with peripheral neuropathy and neuropathic pain. <b>Conclusions</b>: The findings indicate that HIV-tg rats develop peripheral neuropathy and neuropathic pain comparable to those observed in PLWH. BCP is more effective than cannabidiol (CBD) in alleviating HIV-related neuropathic pain. Furthermore, the data suggest that BCP modulates specific proteins that may contribute to its analgesic effects in the HIV-tg model of neuropathic pain, without inducing central side effects.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063668","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":"Calcifediol Treatment Improves Skin Wound Healing in Vitamin D Deficiency Obese Rats.","authors":"Bárbara Torrecillas-Baena, Victoria Pulido-Escribano, Marta Camacho-Cardenosa, María Dolores Carmona-Luque, Laura De Los Santos Castillo-Peinado, Feliciano Priego-Capote, José Manuel Quesada-Gómez, Gabriel Dorado, María Ángeles Gálvez-Moreno, Antonio Casado-Díaz","doi":"10.3390/pharmaceutics18091175","DOIUrl":"10.3390/pharmaceutics18091175","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Obesity is a major public health problem and a risk factor for numerous diseases. Furthermore, the high prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in obese individuals promotes a state of persistent inflammation and contributes to the development of hard-to-heal skin wounds. Although calcifediol is effective in correcting this deficiency, its effect on cutaneous wound healing in obesity has not been fully established. Thus, the objective of this work has been to evaluate the impact of calcifediol treatment on wound healing in an animal model of obesity with vitamin D deficiency. <b>Methods:</b> Wistar rats fed a high-fat, vitamin D-deficient diet were subjected to dorsal skin wounds. One group received calcifediol treatment for 14 days. Serum 25(OH)D levels, wound closure rate, histological parameters, and molecular markers related to inflammation were analyzed. <b>Results:</b> Calcifediol significantly increased serum 25(OH)D levels and accelerated wound closure compared to untreated animals. It also improved re-epithelialization, reduced the depth and extent of the lesions, and promoted collagen deposition. Furthermore, it increased the expression of anti-inflammatory markers (IL-10 and CD163) and decreased the infiltration of CD68+ macrophages, indicating a more efficient resolution of the inflammatory response. <b>Conclusions:</b> Calcifediol supplementation improves cutaneous wound healing in obesity with 25(OH)D deficiency by accelerating wound closure, promoting extracellular matrix remodeling, and modulating the inflammatory response, supporting its use as a complementary strategy to enhance tissue repair in conditions of obesity and vitamin D deficiency.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063637","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":"Developing a Method to Quantify Swelling Force Generated by the Osmotic Pump Tablet Push Layer.","authors":"True L Rogers, Stephanie Robart, Thomas Watson, Rhea Wang, Harold Bernthal, Vahid Ahmadi","doi":"10.3390/pharmaceutics18091174","DOIUrl":"10.3390/pharmaceutics18091174","url":null,"abstract":"<p><p><b>Background/Objectives</b>: A push-pull osmotic pump (PPOP) tablet is a controlled-release delivery system consisting of a bilayer tablet (push layer/pull (drug) layer), coated within a selectively permeable barrier membrane, and containing a laser-drilled orifice in the pull layer side of the barrier. Aqueous media permeates across the barrier membrane and into the bilayer tablet core. The push layer swells axially, creating force and acting like a piston to drive the active pharmaceutical ingredient (API) dosage through the laser-drilled orifice. The primary purpose of this study was to develop a method to quantitate swelling force generated by the PPOP push layer. <b>Methods</b>: A key challenge was devising measurement methodology that most closely represented continuous PPOP push-layer swelling force exerted in the axial dimension over time, so the method setup was adjusted until attaining what closely approximated PPOP push-layer swelling-force dynamics within the delivery system. After some adjustments, swelling forces were measured from PPOP push layers containing various polyethylene oxide (PEO) molecular weight (MW) grades. <b>Results</b>: The most representative configuration was a cylindrical holder fully submerged in water with the push-layer compact situated at the bottom of the holder. This setup constrained the push layer to swell in the axial dimension. The optimal setup also allowed the texture analyzer to continuously measure push-layer swelling force over 24 h, representing typical duration of functionality. Quantitative analysis of the swelling force vs. time profiles demonstrated comparable force generation over 24 h from the 4, 5, and 7,000,000 MW grades of PEO. Swelling force decreased in near-linear fashion, from push layers formulated with PEO 4,000,000 down to PEO 100,000. <b>Conclusions</b>: The optimal setup enabled discriminatory quantification of push-layer swelling force for PEO MW grades spanning from 100,000 up to 4,000,000 Daltons. Furthermore, the method demonstrated why the 4, 5, and 7,000,000 MW grades of PEO are recommended for use in the PPOP push layer, given that these three highest MW grades delivered comparable swelling force over 24 h. Finally, the method provides new quantitative insight into the push-layer swelling force that is necessary, over the duration of the dosing interval, to deliver the active dosage from the PPOP tablet.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063470","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":"Non-Systemic Oral Cellulose-Based Superabsorbent Hydrogels for Weight Management: Potential Drug-Device Interactions Estimated by a Simplified In Vitro Assay.","authors":"Eliana Panteca, Ivo Surano, Christian Demitri, Yishai Zohar, Marta Madaghiele, Alessandro Sannino","doi":"10.3390/pharmaceutics18091173","DOIUrl":"10.3390/pharmaceutics18091173","url":null,"abstract":"<p><p><b>Background/Objectives:</b> A technological platform of non-systemic oral cellulose-based superabsorbent hydrogels (CB-SAHs) has been recently developed as novel therapeutics for treating obesity. Further clinical advancement of CB-SAH candidates from this platform requires evaluating their potential impact on the absorption of co-administered drugs. <b>Methods:</b> In this work, we developed a simplified in vitro assay to assess whether and to what extent given CB-SAHs may interact with co-administered drugs. We selected two different CB-SAHs and tested them in contact with various solubilized drug substances under simulated gastrointestinal conditions. A total of 23 drugs were chosen among those that could be used to treat frequent conditions associated with excess weight (e.g., type 2 diabetes) or to deal with common therapeutic needs (e.g., pain relief). Final drug recovery (FDR) in the simulated intestinal medium was quantified using UV-Vis spectroscopy to assess drug-hydrogel interactions. <b>Results:</b> While most drugs achieved an average FDR exceeding 80% with both hydrogels, six compounds exhibited lower FDR values (~68-78%) with at least one CB-SAH, indicating stronger, specific drug-hydrogel interactions. Notably, the FDR measured for metformin with both CB-SAHs (~94%) was consistent with previous clinical findings demonstrating negligible metformin-CB-SAH interaction. <b>Conclusions:</b> Although simplified, the in vitro assay shows promise as an exploratory screening tool to identify specific drug-CB-SAH interactions that warrant subsequent clinical evaluation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063462","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":"Long-Term Survival Heterogeneity Across PD-L1-Defined Subgroups in Pembrolizumab-Treated Non-Small-Cell Lung Cancer: A Model-Based Analysis.","authors":"Heungjo Kim, Sungjae Lee, Hongjae Lee, Ji Woo Lim, Tahir Sher, Chanwoo Kim, Junjeong Choi, Sun Min Lim, Min Jung Chang","doi":"10.3390/pharmaceutics18091177","DOIUrl":"10.3390/pharmaceutics18091177","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Immune checkpoint inhibitors have substantially improved survival outcomes in non-small-cell lung cancer (NSCLC). However, survival heterogeneity across PD-L1-defined and other clinically relevant patient subgroups remains incompletely characterized, limiting subgroup-specific interpretation of pembrolizumab outcomes within a precision oncology framework. In this study, we quantified survival heterogeneity and estimated long-term outcomes of pembrolizumab using reconstructed clinical trial data. <b>Methods</b>: A systematic review identified 36 trials in advanced NSCLC. Individual time-to-event and censoring records were reconstructed from published Kaplan-Meier curves, while patient-level clinical and demographic covariates were stochastically assigned according to trial-level summary distributions. Parametric time-to-event models were developed for overall survival (OS) and progression-free survival (PFS) across programmed death-ligand 1 (PD-L1) tumor proportion score subgroups. Model performance was evaluated using bootstrap analyses and external validation, and model-based simulations were conducted to project survival for up to 10 years. <b>Results</b>: A total of 7165 reconstructed time-to-event records for OS and 6730 for PFS were included in the analyses. Model-predicted survival outcomes varied across clinically relevant characteristics, with higher PD-L1 expression, treatment-naïve status, non-squamous histology, and combination therapy generally associated with more favorable outcomes. Long-term projections demonstrated substantial heterogeneity across covariate-defined subgroups, with projected 10-year OS probabilities ranging from 7.2% to 18.0% among treatment-naïve subgroups. <b>Conclusions</b>: These findings provide a quantitative characterization of subgroup-specific survival heterogeneity and long-term outcomes in pembrolizumab-treated NSCLC, supporting a more refined interpretation of treatment outcomes in the context of precision oncology.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063856","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":"Pharmacological Potential of Selenoproteins in the Regulation of Oxidative Stress in Liver Diseases.","authors":"Elena G Varlamova","doi":"10.3390/pharmaceutics18091167","DOIUrl":"10.3390/pharmaceutics18091167","url":null,"abstract":"<p><p><b>Background:</b> Pathological activation of oxidative metabolism is a universal catalyst for liver parenchyma destruction. While physiological pools of reactive oxygen and nitrogen species (ROS/RNS) regulate hepatic regeneration and cellular respiration, decompensation of endogenous antioxidant systems induces cascading damage across hepatocytes, sinusoidal endothelial cells, Kupffer macrophages, and hepatic stellate cells. Current therapies against liver fibrosis, cirrhosis, and hepatocellular carcinoma remain suboptimal, necessitating the identification of novel, druggable molecular targets. <b>Focus:</b> This review synthesizes current evidence on ROS-driven necroinflammatory and degenerative cascades and evaluates the multi-level protective potential of the selenoprotein family. <b>Evidence:</b> Selenoproteins function as a highly heterogeneous network where specific members are vital for cell survival (e.g., GPX4 in preventing ferroptosis), while others exhibit stage-dependent expression throughout progression from inflammation to malignancy. <b>Conclusions:</b> In addition to directly scavenging free radicals, selenoproteins modulate endoplasmic reticulum stress, metabolic remodeling, and immune responses. A more complete understanding of the important role of selenoproteins in regulating liver pathological processes, particularly their antioxidant function, allows them to be considered as promising potential targets for the further development of pharmacotherapeutic strategies for the treatment of chronic liver diseases.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063701","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":"Salcaprozate Sodium as a Permeation Enhancer-Mechanism, Applications and Unresolved Questions.","authors":"Boris Dinkov, Nikolinka Koleva, Galya Stavreva","doi":"10.3390/pharmaceutics18091171","DOIUrl":"10.3390/pharmaceutics18091171","url":null,"abstract":"<p><p>Oral absorption remains challenging for peptides, proteins, and other drug substances with limited stability or permeability. Sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC), also known as salcaprozate sodium, is an oral permeation enhancer used in approved drug products. This review summarizes the physicochemical properties and mechanisms of action of SNAC and evaluates its clinical and emerging preclinical applications. A structured literature search was conducted in PubMed and Scopus, supplemented as needed with ClinicalTrials.gov and regulatory documents. The search covered 2015-2026, with earlier key publications included where necessary for historical context. After screening, 71 sources were included in the narrative synthesis. The review examines the proposed mechanisms of SNAC-mediated permeation enhancement, including local pH modulation, membrane-mediated effects, peptide self-association, and context-dependent effects on epithelial permeability. Clinical evidence is summarized for oral semaglutide, cyanocobalamin, unfractionated heparin, ibandronate, and investigational peptide products. Emerging applications beyond metabolic diseases are discussed together with formulation strategies and safety considerations. Recent preclinical findings suggesting changes in gut microbiota and inflammatory markers are critically evaluated in the context of the available clinical safety experience, while their relevance to humans remains unconfirmed. Overall, SNAC reliably enhances permeation in vitro and in vivo, yet the resulting oral bioavailability remains low and variable and is strongly dependent on payload, formulation, and gastrointestinal conditions. Long-term safety and the clinical relevance of recent preclinical microbiome findings remain important areas for future investigation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063292","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":"Ethyl Lauroyl Arginate-Integrated Lipid Nanoparticles as a Multifunctional Non-Antibiotic Platform: Physicochemical Stability, Follicular Penetration, and Broad-Spectrum Activity Against Canine Skin Pathogens.","authors":"Kittipat Supchukun, Teerapong Yata, Jakarwan Yostawonkul, Benchaphorn Limcharoen, Sayamon Srisuwatanasagul","doi":"10.3390/pharmaceutics18091165","DOIUrl":"10.3390/pharmaceutics18091165","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Canine superficial pyoderma is one of the most common dermatological diseases in dogs and is increasingly complicated by antimicrobial resistance. This study aimed to develop ethyl lauroyl arginate-integrated lipid-based nanoparticles (LAE-LBNs) as a non-antibiotic topical delivery platform and to evaluate their physicochemical stability, skin localization, and antimicrobial activity against clinically relevant canine skin pathogens. <b>Methods:</b> LAE-LBNs were prepared using high-shear homogenization followed by probe ultrasonication and characterized for particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency, and storage stability. Antimicrobial activity was evaluated against methicillin-susceptible <i>Staphylococcus pseudintermedius</i> (MSSP), methicillin-resistant <i>S. pseudintermedius</i> (MRSP), and <i>Malassezia pachydermatis</i>. The ex vivo distribution of Nile Red-labeled formulations was assessed in porcine ear skin using fluorescence microscopy. <b>Results:</b> The optimized 5% LAE-LBN formulation exhibited a relatively small particle size, narrow size distribution, strongly positive surface charge (+46.49 mV), encapsulation efficiency exceeding 99%, and favorable physicochemical stability over two months. Fluorescence associated with the labeled LAE-LBN formulation was observed in the stratum corneum, viable epidermis, and hair follicles, whereas the aqueous control formulation was predominantly confined to the stratum corneum. LAE-LBNs exhibited bactericidal and fungicidal activity against MSSP, MRSP, and <i>M. pachydermatis</i>, with an MBC or MFC of 12.2 µg/mL. These endpoints were identical to those obtained for aqueous LAE, indicating that incorporation into the lipid-based nanocarrier preserved the antimicrobial activity of LAE. <b>Conclusions:</b> LAE-LBNs combined favorable physicochemical properties, follicular localization, and activity against bacterial and fungal canine skin pathogens. These findings support their further investigation as a non-antibiotic topical delivery platform for canine superficial pyoderma.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063600","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":"Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation.","authors":"Eleonora Sofia Cama, Giada Botti, Sara Perteghella, Laura Catenacci, Fahad Khan Tareen, Sarah Beggiato, Maria Cristina Bonferoni, Luca Ferraro, Milena Sorrenti, Alessandro Dalpiaz","doi":"10.3390/pharmaceutics18091168","DOIUrl":"10.3390/pharmaceutics18091168","url":null,"abstract":"<p><p><b>Background:</b> Dimethyl fumarate (DMF) is an approved therapeutic agent for the treatment of multiple sclerosis, known for its anti-inflammatory and neuroprotective properties. However, its oral administration is often accompanied by gastrointestinal side effects, limiting its therapeutic potential. In the present study, a novel nanoemulsion (NE) formulation was developed and characterized with the aim of enhancing DMF exposure in the cerebrospinal fluid (CSF) following intranasal administration. <b>Methods:</b> The formulation was prepared via a self-emulsification method using geraniol (GER) as the oil phase, selected for its antioxidant properties, and chitosan oleate as a mucoadhesive stabilizer and absorption promoter. Physicochemical characterization, in vitro release, RPMI 2650 cell cytotoxicity, and permeability were evaluated. Finally, an optimized NE (1.08 ± 0.02 mg/mL DMF and 0.28 ± 0.01 mg/mL GER) was administered intranasally to adult male Sprague-Dawley rats to assess DMF and GER exposure in the CSF. <b>Results:</b> The NEs exhibited optimal physicochemical properties: a mean particle size of approximately 170 nm, a polydispersity index below 0.3, and a positive zeta potential (above 20 mV). Spectroscopic and thermal analyses confirmed GER and DMF compatibility and a reciprocal enhancement of stability. In vitro drug release studies revealed a fast release profile, with 81% of DMF released within 2 h, aligning with the rapid absorption expected from nasal administration. Cytotoxicity assays showed high biocompatibility (>86% viability up to 50 µM DMF), while permeability studies demonstrated significant absorption, with 60% of DMF and 90% of GER absorbed within 2-3 h, favored by smaller droplet size. In rats, intranasal delivery achieved maximum CSF concentrations of ~8 µg/mL for DMF and ~1.5 µg/mL for GER within 2 h. <b>Conclusions:</b> These findings provide pharmacokinetic proof-of-concept supporting further investigation of this intranasal formulation for CNS delivery of DMF.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063795","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":"Disulfiram's Anti-Inflammatory and Antibacterial Effects in Fixed-Dose Combination Therapy for Scabies.","authors":"Carmen Salavastru, Angela Hernández-Martín, Sanja Bulut, Laura Fernàndez Fajardo, Aymée Robainas Barcia, Maria Lajarin-Reinares","doi":"10.3390/pharmaceutics18091172","DOIUrl":"10.3390/pharmaceutics18091172","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Scabies is a highly contagious parasitic skin infestation in which mite infestation, epidermal barrier disruption, secondary bacterial infection, and local inflammation collectively contribute to disease burden. This study investigated whether disulfiram, a component of a fixed-dose benzyl benzoate formulation, may provide local biological activity relevant to scabies-associated complications. <b>Methods:</b> Ex vivo permeation of the formulation was assessed in dermatomed porcine skin, with disulfiram retention in the stratum corneum and dermatomed skin measured against minimum inhibitory concentrations (MICs) for <i>Staphylococcus aureus</i> and <i>Streptococcus pyogenes</i>. Cytotoxicity of the formulation was evaluated in HEK001 keratinocytes across tested concentrations. In vitro antibacterial activity of disulfiram was tested against both Gram-positive species. Transcriptomic profiling was performed on keratinocytes exposed to the formulation. <b>Results:</b> Benzyl benzoate permeation was measurable in the ex vivo model, whereas disulfiram was not detected in the receptor phase under the experimental conditions. Disulfiram was retained in the stratum corneum and dermatomed skin at concentrations exceeding the MICs observed against <i>S. aureus</i> and <i>S. pyogenes</i>. The formulation was not cytotoxic in HEK001 keratinocytes at any tested concentration. Disulfiram showed in vitro antibacterial activity against both Gram-positive species. Transcriptomic profiling identified differential expression of genes involved in oxidative stress responses, detoxification, glutathione metabolism, innate immune signaling, and inflammatory mediator regulation. <b>Conclusions:</b> These findings support a mechanistic rationale for disulfiram as a locally retained component with potential therapeutic relevance to bacterial infection and keratinocyte inflammation in scabies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063648","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}