International Journal of Pharmaceutics: X最新文献

{"title":"Developing Immunoniosomes (INs): Antibody and Fab conjugations of niosomal nanoparticles via UV-NBS and EDC/NHS chemistry for treating glioblastoma cells","authors":"Nilufer Cakir ,&nbsp;Hatice Oncel ,&nbsp;Aylin Ozkan ,&nbsp;Dilan Bicak ,&nbsp;Sibel Akgun Bas ,&nbsp;Nur Mustafaoglu","doi":"10.1016/j.ijpx.2025.100367","DOIUrl":"10.1016/j.ijpx.2025.100367","url":null,"abstract":"<div><div>Antibody-conjugated nanoparticles (ACNPs), particularly immunoliposomes (ILs), have gained significant attention in cancer treatment due to their enhanced efficacy and superior tissue penetration. However, their high production costs and technical challenges underscore the need for more cost-effective alternatives. Niosomes, with their lower production costs, improved stability, and biocompatibility, have emerged as promising alternatives to liposomes in drug delivery. This study introduces immunoniosomes (INs), a novel class of antibody-conjugated niosomes, through two conjugation strategies: (i) UV-NBS, a site-specific covalent conjugation method utilizing an indole ring structure for moderate binding to the variable regions of antibodies and Fab fragments, and (ii) EDC/NHS chemistry, which conjugates antibodies to carboxylated niosomes via primary amines on lysine sidechains. Bevacizumab, a monoclonal antibody targeting VEGF and approved for the treatment of various cancers including glioblastoma multiforme (GBM), was used as a model therapeutic. Both Bevacizumab and its Fab fragment were conjugated to niosomes and evaluated in U87 glioma cells (overexpressing VEGF) and human umbilical vein endothelial cells (HUVECs) (representing normal VEGF expression). Physicochemical characterization of the conjugated niosomes confirmed hydrodynamic sizes ranging from 100 to 200 nm, neutral surface charge, and dispersity indices below 0.5—properties critical for effective cellular penetration and drug delivery. Cellular toxicity assays, conducted at a 10× dilution from commonly reported concentrations, highlighted the role of the autocrine loop in U87 glioblastoma cells. Importantly, specific Nio-Fab conjugate formulations, created through both site-specific and randomized conjugation strategies, exhibited enhanced cytotoxicity toward U87 cells while sparing healthy endothelial HUVEC cells. In summary, this research establishes novel conjugation strategies to produce stable, site-specific, and randomized antibody-niosomal conjugates with enhanced half-life and selective toxicity against GBM cells. By offering an alternative route for antibody delivery through niosomal nanocarriers, these findings open new avenues for the development of more effective GBM therapeutics, warranting further non-clinical and clinical investigations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100367"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of long-acting riluzole transdermal patch against amyotrophic lateral sclerosis: Mechanistic insights into polyglyceryl-3 dioleate-enhanced drug release and skin permeation","authors":"Yanan Liu,&nbsp;Guixue Chen,&nbsp;Maojian Li,&nbsp;Man Li,&nbsp;Daoxuan Xie,&nbsp;Zheng Luo","doi":"10.1016/j.ijpx.2025.100363","DOIUrl":"10.1016/j.ijpx.2025.100363","url":null,"abstract":"<div><div>Patients with amyotrophic lateral sclerosis (ALS) often experience difficulty swallowing, making oral administration unsuitable for effective treatment. A transdermal drug delivery system (TDDS) offers a long-acting, non-invasive alternative for ALS therapy. In this study, a riluzole transdermal patch capable of sustained release over 72 h was developed. In vitro skin permeation and pharmacokinetic experiments were conducted to evaluate the impact of various factors—including drug loading, type and concentration of chemical penetration enhancers (CPEs), and type of pressure-sensitive adhesive—on riluzole absorption through the skin. The optimized patch formulation contained 17 % (<em>w</em>/w) riluzole and 10 % (w/w) polyglyceryl-3 dioleate (PGD), with an adhesive layer thickness of 111 μm. The final prescription penetration rate of riluzole was found to be 2.96 μg/(h·cm²). Optimized formulation displayed enhanced stability and prolonged pharmacokinetic performance (<em>C</em>_max = 74.34 ± 13.62 ng/mL, MRT_0-<em>t</em> = 34.91 ± 11.31 h). No significant skin irritation was observed. The role of PGD in the in vitro release and in vivo transdermal absorption of riluzole was thoroughly investigated. The results revealed that PGD not only reduced the interaction between riluzole and the pressure-sensitive adhesive, enhancing drug release but also increased the fluidity of skin lipids, leading to improved transdermal absorption. This study provides a comprehensive molecular-level understanding of PGD's effect on riluzole permeation, offering valuable insights for the rational selection of CPEs in the development of riluzole TDDS.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100363"},"PeriodicalIF":5.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Packing and flow performance of binary adhesive mixtures for inhalation of different drug loads and their relationships to aerosolisation","authors":"Anna Simonsson ,&nbsp;Tobias Bramer ,&nbsp;Alex Wimbush ,&nbsp;Göran Alderborn","doi":"10.1016/j.ijpx.2025.100358","DOIUrl":"10.1016/j.ijpx.2025.100358","url":null,"abstract":"<div><div>The aim of this study was twofold. First, to examine the mechanical properties (packing and flow) of a series of adhesive mixtures, consisting of two different lactose carriers and varying concentrations of budesonide, using a range of test methods. Second, to investigate if any of the test methods correlate with the dispersibility of the mixtures, i.e. the fine particle fraction and mass median aerodynamic diameter. The mechanical properties assessed included packing, shearing, permeability and compressibility. Dispersion data were generated using an impactor operated at two pressure drops (0.5 and 4 kPa). To explore correlations between the mixture properties, Principal Component Analysis and Pearson correlation were used as statistical tools.</div><div>The different test methods yielded different property-drug load relationships, which can be classified into two groups: First, packing density and shearing properties, and second, permeability and compressibility. The methods in the first group produced markedly fluctuating property-drug load relationships, characterised by two distinct waves. This type of property-drug load relationship was similar to that observed in the dispersion experiments, and significant correlations were found between shearing properties and dispersibility. Thus, any correlations between mechanical and dispersion properties depend on the choice of the test method used. The underlying cause of this co-variation is the parallel effect of both the blend architecture and the structure of the adhesion layer on mechanical and dispersion properties.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100358"},"PeriodicalIF":5.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pectinase responsive nanoplatform for oral targeted delivery 5-aminosalicylic acid and zinc coordination driven nanozyme in inflammatory bowel disease treatment","authors":"Yiting Lin ,&nbsp;Siqi Fang ,&nbsp;Xinyi Chen ,&nbsp;Xiang Li ,&nbsp;Xinlin Zhao ,&nbsp;Yanwen Wang ,&nbsp;Jing Lu ,&nbsp;Qingdong Ji ,&nbsp;Shuhui Zheng ,&nbsp;Jiafeng Zou ,&nbsp;Chendong Qi ,&nbsp;Feng Gao","doi":"10.1016/j.ijpx.2025.100362","DOIUrl":"10.1016/j.ijpx.2025.100362","url":null,"abstract":"<div><div>Characterized by weight loss, intestinal ulcerations, and diarrhea with blood or mucus, inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic gastrointestinal condition. The rising incidence of IBD is placing pressure on healthcare systems globally. Although the precise etiology remains elusive, the dysregulation between reactive oxygen species (ROS) and hydrogen sulfide (H₂S) is a crucial determinant in the pathogenesis of inflammatory bowel disease (IBD). Though 5-aminosalicylic acid (5-ASA) is effective in the early-stage of IBD, restoring intestinal environmental balance, its use is limited by off-target problem and toxicity. This study introduces a novel oral nano-drug delivery system that improves efficacy and reduces side effects by coordinating 5-ASA with Zn²⁺ to form nanozymes (5-ASA-Zn²⁺, A-Z) and encapsulating them in nanoplatform (A-Z@cHP), which made from chitosan (CS), hyaluronic acid (HA), pectin (PC) and calcium chloride. The nanozymes displayed uniform particle size, stability, and ability to regulate ROS and H₂S. The nanoplatform showed the characteristic of acid resistance, pectinase responsive drug release, low cytotoxicity, and effective targeting <em>via</em> CD44 receptors. In a DSS-induced mouse colitis model, A-Z@cHP significantly improved body weight, disease activity index, colon length, and colonic barrier while reducing inflammation by restoring the balance of ROS and H₂S. Furthermore, the balance restoration of intestinal flora also benefits from the above regulatory effect of nanoparticles. Biosafety evaluations confirmed no significant side effects. In conclusion, this targeted nanoplatform provides a promising new approach for improving the efficacy of 5-ASA against IBD.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100362"},"PeriodicalIF":5.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and applications of exosome-microneedle integrated systems","authors":"Lijie Zheng ,&nbsp;Jiting Sun ,&nbsp;Lusheng Wang ,&nbsp;Zhixian Ding ,&nbsp;Yu Tang ,&nbsp;Mike Dai ,&nbsp;Heng Tang","doi":"10.1016/j.ijpx.2025.100360","DOIUrl":"10.1016/j.ijpx.2025.100360","url":null,"abstract":"<div><div>With the rapid advancement of drug delivery technologies, microneedles (MNs) have emerged as a novel transdermal delivery platform due to their ease of administration, minimally invasive nature, and high efficiency. MNs have demonstrated broad applicability for delivering diverse therapeutic agents, including small molecules, nucleic acids, peptides, and proteins. Exosomes (Exos), a class of extracellular vesicles with unique biological functions and significant clinical potential, have attracted increasing attention in recent years. However, their widespread application is limited by issues such as poor stability, low delivery efficiency, and potential safety and immune risks. The integration of Exos with MNs (Exos-MNs) systems offers a promising strategy to address these challenges. This review provides a comprehensive overview of recent advances in Exos-MNs delivery systems, including the technological advances of MNs, biological characteristics and engineering strategy of Exos, and the construction strategies of Exos-MNs. Additionally, we highlight recent developments in the application of Exos-MNs systems and discuss future perspectives and challenges for their clinical translation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100360"},"PeriodicalIF":5.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring bioadhesion: insight on innovative strategies to investigate bioadhesive scaffolds","authors":"Marta Pollini,&nbsp;Eleonora Bianchi,&nbsp;Marco Ruggeri,&nbsp;Barbara Vigani,&nbsp;Silvia Rossi,&nbsp;Giuseppina Sandri","doi":"10.1016/j.ijpx.2025.100359","DOIUrl":"10.1016/j.ijpx.2025.100359","url":null,"abstract":"<div><div>In the pharmaceutic field, materials with enhanced bioadhesive properties have been widely employed to produce scaffolds with deep interaction and adhesion to the biological surfaces, preventing them from dislocation and promoting cell homing, proliferation and growth. Parallelly, mucoadhesion has been extensively used to increase formulation retention onto the mucosal surface. This review aims to describe the most appropriate and relevant techniques to evaluate scaffolds bioadhesion and mucoadhesion for biomedical application, and more in details, in wound healing treatment. Different methods will be reviewed and described in order to provide an overview of the traditional approaches and the most innovative and recent tools. In addition, critical considerations on the variety of biological substrates that could be used will be reported to underline the different alternatives for testing bioadhesion, including <em>ex-vivo</em> and artificial options. Biomaterials, with a particular focus on bioadhesives, will be presented, as well as the mechanisms that govern bioadhesion and mucoadhesion.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100359"},"PeriodicalIF":5.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model","authors":"Nihal Farid Younes ,&nbsp;Randa Latif ,&nbsp;Alia Badawi ,&nbsp;Khaled Hegazy","doi":"10.1016/j.ijpx.2025.100357","DOIUrl":"10.1016/j.ijpx.2025.100357","url":null,"abstract":"<div><div>The limited bioavailability of orally administered repaglinide presents a significant challenge in diabetes management, which can be addressed by developing a buccoadhesive drug delivery system. In this study, repaglinide-loaded cubosomes were prepared using a top-down approach and optimized via a 3³ Box-Behnken design. The optimized formulation (Opt-RPG-CUB) was characterized for solubilization efficiency (SE%), particle size (PS), zeta potential (ZP), drug release kinetics, and morphology. To further enhance drug delivery, a 2² factorial design was utilized to incorporate varying concentrations of the gelling agents hydroxypropyl methylcellulose or carboxymethyl cellulose into Opt-RPG-CUB, forming repaglinide-loaded cubogels. Upon optimization, the cubogel with the highest desirability function, designated as Opt-RPG-Cubogel, was further evaluated for mucoadhesion, drug release kinetics, rheological properties, ex-vivo buccal permeation, and in-vivo drug permeation by confocal laser scanning microscopy and pharmacodynamic assessment in a streptozotocin-induced diabetic rat model. Results showed that Opt-RPG-CUB exhibited a SE% of 88.01 ± 3.92 %, PS of 252.55 ± 17.18 nm, and ZP of −31.13 ± 1.42 mV, with an extended drug release over 24 h and a cubic nanostructure. Opt-RPG-Cubogel exhibited strong mucoadhesion (&gt;9 h), an extended drug release over 24 h, enhanced mucosal permeation, and improved tissue deposition. Confocal microscopy further confirmed deep mucosal penetration, while in-vivo studies demonstrated a significant reduction in blood glucose levels compared to the control. Overall, these findings highlight the potential of Opt-RPG-Cubogel as a promising buccoadhesive drug delivery system for efficient type II diabetes management.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100357"},"PeriodicalIF":5.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal glytrexate formulation: improving antitumour efficacy and minimizing toxicity in breast cancer therapy","authors":"Wenli He ,&nbsp;Meng Yan ,&nbsp;Yue Li ,&nbsp;Jianchao Wang ,&nbsp;Jianing Yang ,&nbsp;Chaoxing He ,&nbsp;Shaokun Yang ,&nbsp;Deying Cao ,&nbsp;Jing Bai ,&nbsp;Lei Wang ,&nbsp;Bai Xiang","doi":"10.1016/j.ijpx.2025.100356","DOIUrl":"10.1016/j.ijpx.2025.100356","url":null,"abstract":"<div><div>Cancer remains a critical global health challenge with increasing incidence rates. This study reports the first successful encapsulation of glytrexate (GTX), a novel 6-substituted-pyrrolo [2,3-d] pyrimidine compound, into liposomes. This innovative formulation increases the stability, half-life, and bioavailability of GTX while significantly reducing toxicity. GTX liposomes, with a uniform spherical shape and an average particle size of 121.7 ± 2.9 nm, demonstrated a satisfactory encapsulation efficiency (24.2 ± 0.99 %). Compared to the free drug, GTX liposomes exhibited significantly enhanced inhibitory effects on 4 T1, A549, and MCF-7 cells in vitro. The pharmacokinetic analysis showed prolonged circulation (T_1/2: 3.82 h vs. 1.86 h) and increased systemic exposure (AUC_0–∞: 31975.79 vs. 11,545.86 μg·h/L). In vivo studies further confirmed their efficacy, as they substantially reduced tumour growth by 50 %, decreasing lung metastasis in 4 T1 cell models, and minimizing GTX-related side effects. These findings highlight the potential of liposomal GTX formulations to improve breast cancer treatment outcomes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100356"},"PeriodicalIF":5.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of fenticonazole nitrate-loaded cubogel for the management of vaginal candidiasis","authors":"Sadek Ahmed ,&nbsp;Osama Saher ,&nbsp;Heba Attia ,&nbsp;Abdurrahman M. Fahmy ,&nbsp;Islam M. Adel","doi":"10.1016/j.ijpx.2025.100355","DOIUrl":"10.1016/j.ijpx.2025.100355","url":null,"abstract":"<div><div>Vaginal candidiasis is a medical condition that affects large majority of the women at least once in their lifetime. The condition manifests with itching, irritation, and discharges which is troublesome for women during mundane activities. The purpose of this research was to formulate and evaluate the physicochemical properties and drug permeation of Fenticonazole-loaded cubogel through vaginal mucosa. Concisely, the drug-loaded cubosomes were prepared via hot dispersion emulsification technique. Following, the percent drug entrapment efficiency, particle size, polydispersity index, and zeta potential of the cubosomes were determined. Optimization criteria involved maximizing entrapment efficiency (EE %) and zeta potential (ZP), while maintaining a nanoscale particle size to ensure colloidal stability. The optimized formulation exhibited a high desirability score of 0.933 with EE % of 85.32<span><math><mo>±</mo></math></span>2.34 %, PS of 169<span><math><mo>±</mo></math></span>0.85 nm, PDI of 0.29<span><math><mo>±</mo></math></span>0.02, and ZP of −24.40<span><math><mo>±</mo></math></span>1.27 mV. In addition, 86.77<span><math><mo>±</mo></math></span>3.79 % of Fenticonazole nitrate was released from the optimum cubosomal formulation after 8 h. Cubical nanovesicles were revealed via transmission electron microscope while infrared spectroscopy revealed the lack of interaction between the used components. Stability was unchanged upon storage for three months. The rheogram of the optimum formulation-loaded cubogel suggested a shear-thinning behavior. Additionally, the optimum cubogel demonstrated higher biofilm inhibitory effect compared to the drug suspension. Similarly, both, ex vivo permeation and confocal laser scanning, suggested the enhanced vaginal epithelium permeability and the deeper vaginal mucosa penetration of the optimum cubogel, compared to the drug suspension and aqueous Rhodamine B carbopol gel, respectively. Histopathological assessment concluded with the safety of the cubogel on the vaginal mucosal epithelium and underlying tissue.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100355"},"PeriodicalIF":5.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing losartan potassium against rheumatoid arthritis via transdermally-delivered leciplexes: Accentuated efficacy through modulation of angiotensin II/AT1R/AT2R axis","authors":"Amira A. Hussein ,&nbsp;Basmah N. Aldosari ,&nbsp;Randa M. Zaki ,&nbsp;Obaid Afzal ,&nbsp;Adel A. Ali ,&nbsp;Heba M. Aboud ,&nbsp;Yasmin M. Ahmed ,&nbsp;Demiana M. Naguib","doi":"10.1016/j.ijpx.2025.100354","DOIUrl":"10.1016/j.ijpx.2025.100354","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory ailment which preferentially impacts the synovial membranes of joints and ultimately triggers cartilage and bone erosion. Angiotensin II (Ang II) participates in the pathogenesis of RA; hence, Ang II receptor blockade, accomplished through a specific inhibitor such as losartan potassium (LST), may confer an effective therapeutic avenue for RA. This study aimed to develop, optimize, and characterize LST-loaded leciplexes (LST-LPXs) to ameliorate its bioavailability and prolong its therapeutic efficacy for combating RA. To accomplish this objective, LST-LPX dispersions were assembled through a single-step process and optimized via D-optimal design for various physicochemical traits employing Design-Expert® software. Also, pharmacokinetic studies were explored in rats. Additionally, in complete Freund's adjuvant-induced RA in Wistar rats, RF, COMP, NADPH oxidase, NO, IL-6, TNF-α, besides Ang II and its receptors (AT1R &amp; AT2R) were measured. The optimum LST-LPXs formulation elicited acceptable entrapment efficiency (88.05%), nano-scaled spherical morphology (246.71 nm), controlled release over 24 h (86.33%), and adequate permeation properties through the skin (417.83 μg/cm²). The pharmacokinetic analysis disclosed a snowballed bioavailability of the optimized LST-LPXs gel by 3.08- and 1.2-fold versus the oral solution and crude gel, respectively. The optimum LST-LPXs gel divulged accentuated anti-arthritic effects, evidenced by significant suppression of rheumatoid, oxidative stress, and inflammatory biomarkers coupled with corrections of AT1R and AT2R protein expression. Practically, the current findings proposed a compelling proof-of-principle that the transdermal LST-LPXs could serve as a non-invasive promising nanoparadigm for RA tackling.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100354"},"PeriodicalIF":5.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}