European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Insight in the role of resistant starch and Eudragit S 100 in a coating for controlled release in the colonic region","authors":"Sien Dedroog ,&nbsp;Jiabi Ouyang ,&nbsp;Elise Vaes ,&nbsp;Filip Willemse ,&nbsp;Sune Klint Andersen ,&nbsp;Guy Van den Mooter","doi":"10.1016/j.ejpb.2025.114818","DOIUrl":"10.1016/j.ejpb.2025.114818","url":null,"abstract":"<div><div>A dual trigger coating was designed by Ibekwe et al. to achieve site-specific delivery of therapeutics to the colon. It consists essentially of Eudragit® S 100 (EU S 100), a polymer that dissolves above pH 7, and resistant starch, which can only be degraded by enzymes produced by colonic bacteria. Both components should maintain the integrity of the coating until reaching the colonic region and ensure drug release when reaching it. The contribution of these components was investigated in the present study by permeability testing and enzymatic degradation testing of free polymer films produced using an in-house built spraying device.</div><div>Diffusion testing of EU S 100 films showed no impact of the pH (2, 4, 6) and plasticizer levels (25, 30, 35 % w/w triethyl citrate (TEC)) on the permeability of the films. The permeability of the resistant starch-Eudragit® S 100 (RS-EU S 100) films was also not affected by the pH, however, the permeability coefficient of films containing 35 % w/w TEC was significantly higher for all pH levels. Incubating the RS-EU S 100 films with enzyme resulted in a higher permeability for films with 25 % w/w TEC, yet the presence of enzyme had no effect on the permeability of 35 % w/w TEC films. For the 25 % w/w TEC films, even if EU S 100 does not dissolve (pH &lt; 7), the resistant starch in the RS-EU S 100 film can be enzymatically degraded.</div><div>Using n-butanol in the preparation process of the RS-EU S 100 films resulted in a lower permeability coefficient compared to the RS-EU S 100 films without n-butanol for all pH and plasticizer levels. n-Butanol forms a V-type complex with amylose, which makes the films less susceptible to enzymatic degradation.</div><div>The permeability and susceptibility to enzymatic degradation of the RS-EU S 100 coating can be adapted by altering the amount of plasticizer and the use of n-butanol during the production process.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114818"},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759563","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 airway biological barriers: Implications for IgG-based therapeutics in respiratory infections","authors":"Gabrielle Pichon ,&nbsp;Christelle Parent ,&nbsp;Stefanie Graeter ,&nbsp;Alexander Schaub ,&nbsp;Anna Schnell ,&nbsp;Thomas Sécher ,&nbsp;Nathalie Heuzé-Vourc’h","doi":"10.1016/j.ejpb.2025.114817","DOIUrl":"10.1016/j.ejpb.2025.114817","url":null,"abstract":"<div><div>Despite the considerable value of prophylactic vaccines and post-exposure antimicrobials, respiratory infections represent a huge burden. The control of bacterial respiratory infections is compromised by the alarming rise in antibiotic resistance, which underscores the requirement for alternative or complementary interventions. Recent studies have demonstrated that anti-infective IgG-based therapeutics can have an important role in tackling pathogens, and that inhalation is a promising route to target respiratory infections in the lung. Here, we investigated the impact of physical and biological barriers encountered by inhaled IgG during respiratory infections. These include hyper-production and thickening of mucus, as well as bacteria embedded in biofilm. Experiments using artificial bronchiectasis-like mucus showed reduced mobility and pathogen-binding of IgG as compared to artificial mucus with healthy characteristics. Our findings highlight the reduced ability of IgG to effectively opsonize pathogens and trigger effector functions during respiratory infections, such as the ones associated to bronchiectasis. In parallel, IgG was able to disrupt <em>P.aeruginosa</em> biofilm integrity upon repeat administrations <em>in vitro</em>. These results support the use of locally applied human polyclonal IgG in infection-driven chronic lung diseases and highlight the challenges to consider for the development of inhaled IgG.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114817"},"PeriodicalIF":4.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721911","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":"Better GRAS than sorry: Excipient toxicity in pulmonary formulations","authors":"Eleonore Fröhlich","doi":"10.1016/j.ejpb.2025.114814","DOIUrl":"10.1016/j.ejpb.2025.114814","url":null,"abstract":"<div><div>Similar to other routes of administration, pulmonary formulations typically contain excipients. The panel of substances that can be used in pulmonary formulations is limited compared to other routes of administration, and most of them have the generally regarded as safe (GRAS) status. New excipients must undergo in vitro and complete in vivo testing to be approved by regulatory authorities. The toxic effects induced by excipients contained in the most common pulmonary formulations (dry powder inhalers, pressurized metered dose inhalers, and nebulizers) were summarized to compare the cytotoxic effects to the approved concentrations. The hypothesis was that a concentration much higher than the approved one could serve as an indicator of the safety of the compound. While the cytotoxic concentration of many excipients was higher than the approved concentration, the opposite was found for some of them. For most of these compounds, adverse lung effects were reported with long-term administration or in specific populations. This suggests that concentrations lower than the cytotoxic threshold are unlikely to cause adverse respiratory effects. Combining excipients can increase toxic effects, but few studies address this. Since neither cytotoxicity testing nor animal testing can reliably identify toxic concentrations of excipients, additional in vitro tests have been proposed.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"215 ","pages":"Article 114814"},"PeriodicalIF":4.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717758","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":"HDL and LDL-bioinspired nanocarriers in acellular targeted delivery of Icariin for cardiac repair post myocardial infarction","authors":"Nermeen H. Kamal ,&nbsp;Lamia A. Heikal ,&nbsp;Basant A. Bakr ,&nbsp;Maged W. Helmy ,&nbsp;Ossama Y. Abdallah","doi":"10.1016/j.ejpb.2025.114816","DOIUrl":"10.1016/j.ejpb.2025.114816","url":null,"abstract":"<div><div>Myocardial infarction (MI) is a major ischemic heart condition that leads to the loss of billions of cardiomyocytes, triggering adverse ventricular remodeling and fibrotic tissue formation, which can ultimately result in heart failure. Current treatments fail to address cardiomyocyte loss, prompting interest in cardiac regeneration strategies. Although cell-based therapies have gained attention, they face limitations such as poor cell survival and engraftment. Acellular nanoformulations represent a promising alternative. In this study, protein-free bioinspired lipid nanoparticles mimicking low- and high-density lipoprotein; LDL and HDL—namely LDE and HDA—were developed and loaded with the phytomedicine Icariin. Both systems demonstrated high encapsulation efficiency (&gt;90 %), favorable drug release profiles, and good serum stability. In vitro, LDE and HDA exhibited superior cellular uptake in H9c2 cells and significantly improved cell viability in doxorubicin-treated cultures compared to free Icariin. Pretreatment with LDE-Icariin effectively reduced cardiomyocyte apoptosis following doxorubicin exposure. Biodistribution analysis revealed enhanced targeting of infarcted myocardium by HDA over LDE in a rat MI model. Moreover, HDA markedly reduced cardiac damage and promoted regeneration more effectively than LDE. These findings highlight HDA and LDE as cost-effective, bioinspired nanoformulations for cardiac repair, with HDA showing superior targeting and therapeutic performance.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114816"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703676","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":"Age-dependent oral drug absorption in children: Assessment of a bottom-up modelling approach","authors":"Fabian Winter,&nbsp;Jonas Lange,&nbsp;Sandra Klein","doi":"10.1016/j.ejpb.2025.114815","DOIUrl":"10.1016/j.ejpb.2025.114815","url":null,"abstract":"<div><div>Paediatric drug development poses significant challenges due to the unique physiological and ethical considerations in children. Physiologically Based Pharmacokinetic (PBPK) modelling has emerged as a valuable tool for predicting paediatric drug absorption and optimising dosing strategies. This study aimed to refine PBPK modelling for paediatric applications by developing a customised PK-Sim-based paediatric PBPK (pPBPK) model for four drugs that are part of the Model List of Essential Medicines for Children by the World Health Organisation: paracetamol, ibuprofen, darunavir, and itraconazole. The model incorporated age-specific gastrointestinal parameters for four paediatric age groups, minimising the need for parameter interpolation or scaling. The effect of food on drug absorption was investigated by extending the absorption model to account for bile and excipient solubilisation. A literature review identified gaps in the understanding of paediatric intestinal parameters necessary for pPBPK modelling. Biorelevant <em>in vitro</em> dissolution and solubility data were integrated to enhance prediction accuracy. Validation with clinical pharmacokinetic data demonstrated the model’s reliability across different paediatric age groups. Sensitivity analyses highlighted the influence of gastric emptying time, small intestinal transit, and bile salt concentration on drug pharmacokinetics. This research underscores the potential of pPBPK modelling to inform paediatric dosing strategies while addressing current gaps and challenges.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114815"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706872","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 an ophthalmic solution combining allogenic plasma with protective excipients for enhanced therapeutic role in the management of ocular surface diseases","authors":"Agnès Roche ,&nbsp;Philip Chennell ,&nbsp;Frédéric Chiambaretta ,&nbsp;Anne Françoise Serre-Sapin ,&nbsp;Mathieu Wasiak ,&nbsp;Yassine Bouattour ,&nbsp;Valentin Bailly-De-France ,&nbsp;Anne Fogli ,&nbsp;Julie Durif ,&nbsp;Régine Quinard ,&nbsp;Mireille Jouannet ,&nbsp;Vincent Sapin ,&nbsp;Valérie Sautou","doi":"10.1016/j.ejpb.2025.114813","DOIUrl":"10.1016/j.ejpb.2025.114813","url":null,"abstract":"<div><div>Ocular surface diseases (OSDs) are characterised by an instability of the tear film. In severe cases, these disorders have been improved by using human serum or plasma formulated into eye drops. These blood-derived-products present a biological composition similar to that of tears and contain beneficial factors that modulate inflammation and tissue regeneration. However, the supply of blood derivatives remains a challenge due to the potential microbiological risk, the quality and inter-individual heterogeneity of the biological samples used, and logistical difficulties. Thus, the idea behind this work was to use a standardised blood-derived product produced and checked industrially from a pool of donors, and to combine it with protective excipients known for their lubricating, anti-inflammatory, and regenerative properties offering new treatment opportunities for OSDs. Attention was also given to the non-bioaccumulative nature of the excipients. In order to select the concentrations of different compounds of interest in the ophthalmic solution, a design of experiment was used to establish a formulation with physicochemical properties (pH, osmolality, turbidity, viscosity) compatible with good ocular tolerance. Once defined, a physicochemical stability study testing pH, osmolality and dosage of biological factors, was carried out using the storage conditions usually used in clinical practice. A comparator without the additional compounds was also tested. The final formulation consisted of 20 % allogenic plasma, 0.5 % sodium hyaluronate (HS), 3 % trehalose (TH), 0.2 % chondroitin sulfate (CS) and 0.5 % sodium chloride (NaCl) (m/v). Its physicochemical properties should allow for good ocular tolerance. The data from the preliminary stability study favours storage at −20 °C for some of the biological factors measured.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114813"},"PeriodicalIF":4.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687079","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":"Powder-attached microneedles for the stable and effective transdermal delivery of clinically validated mRNA-LNP vaccine","authors":"Ji Seok Kim ,&nbsp;Na-Eun Kim ,&nbsp;Jung-ah Choi ,&nbsp;In-Jeong Choi ,&nbsp;Jeong-Eun Choi ,&nbsp;Aram Kang ,&nbsp;Danbi Kwon ,&nbsp;Mihwa Lim ,&nbsp;Jooyoung Kim ,&nbsp;Seung-Ki Baek ,&nbsp;Manki Song ,&nbsp;Yoon-Jae Song ,&nbsp;Jung-Hwan Park","doi":"10.1016/j.ejpb.2025.114811","DOIUrl":"10.1016/j.ejpb.2025.114811","url":null,"abstract":"<div><div>Microneedle-based delivery offers a promising strategy for administering mRNA-lipid nanoparticle (mRNA-LNP) vaccines via the skin; however, maintaining mRNA-LNP integrity and achieving effective immune responses remain challenging. This study presents a clinically relevant microneedle platform for the transdermal delivery of clinically validated mRNA-LNP vaccines using powder-attached microneedles (P-MAP) and coated microneedles (C-MAP). The mRNA-LNP vaccine, based on the formulation of Moderna’s clinically approved product, was prepared without alteration in their composition or manufacturing method. Lyophilization with stabilizers enabled the production of structurally preserved mRNA-LNP powders, which were physically attached onto the adhesive silicone surface of solid microneedles.</div><div>To evaluate delivery efficiency and quality, three key parameters were assessed: delivery efficiency (D), mRNA-LNP integrity (I), and release kinetics (R). Integrity (I) showed a strong correlation with humoral immune responses and <em>in vivo</em> protective efficacy. P-MAP exhibited a high I value along with rapid mRNA-LNP release, leading to efficient immune activation, complete protection, and efficient viral clearance in mice, whereas C-MAP, despite achieving comparable delivery efficiency, showed reduced structural integrity and slow-release kinetics, resulting in diminished immune responses and no protective effect. The lyophilized powder formulation also retained mRNA-LNP potency for over six months at 4 °C, demonstrating superior storage stability compared to conventional liquid formulations. Furthermore, this system significantly reduced off-target biodistribution to the liver, indicating a favorable safety profile.</div><div>These findings emphasize the need to optimize formulation stability and release kinetics for microneedle-based mRNA vaccine platforms. P-MAP provides a stable and clinically relevant strategy for safe and effective delivery of mRNA-LNP vaccine.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114811"},"PeriodicalIF":4.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680803","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":"Evaluating the efficacy of nintedanib-invasomes as a therapy for non-small cell lung cancer","authors":"Tamer Mohamed Mahmoud ,&nbsp;Mohamed AbdElrahman ,&nbsp;Mary Eskander Attia ,&nbsp;Marwa M. Nagib ,&nbsp;Amr Gamal Fouad ,&nbsp;Amany Belal ,&nbsp;Mohamed A.M. Ali ,&nbsp;Nisreen Khalid Aref Albezrah ,&nbsp;Shatha Hallal Al-Ziyadi ,&nbsp;Sherif Faysal Abdelfattah Khalil ,&nbsp;Mary Girgis Shahataa ,&nbsp;Dina M. Mahmoud","doi":"10.1016/j.ejpb.2025.114810","DOIUrl":"10.1016/j.ejpb.2025.114810","url":null,"abstract":"<div><div>Nintedanib (NDB) is a crucial tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer (NSCLC). However, its oral administration results in limited uptake of NDB by the lungs, necessitating high and frequent dosages, which leads to severe systemic adverse effects and poor bioavailability. To address these issues, a nasal formulation of NDB-invasomes (NLI) was developed as a potential therapy for NSCLC, aiming to improve the sustainability, targeting, bioavailability, and efficacy of NDB. Utilizing design expert software, various formulations were created and optimized. Additionally, analyses were performed on the cytotoxicity, bioavailability, targeting, and toxicity of the optimized NLI formulation. The chosen formulation contained 1.723 % phospholipids, 1.5 % cineole, and 1 % ethanol. The optimized NLI formulation enhanced the sustainability and bioavailability of free NDB by 55 % and 7.93-fold, respectively. Targeting studies indicated that the NLI formulation could achieve a more localized accumulation of NDB in the lungs. Furthermore, the optimized NLI formulation demonstrated greater anticancer efficacy against A549 lung cancer cells than free NDB. Histopathological analysis of the lungs in the optimized NLI group revealed no signs of toxicity. These findings suggest that the nasal NLI formulation is a promising option for treatment of NSCLC.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114810"},"PeriodicalIF":4.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658782","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":"Synergistic approach of salt formation and polymer-mediated stabilization to enhance the biopharmaceutical performance of Mebendazole","authors":"Ridhima Singh ,&nbsp;Mehak Juneja ,&nbsp;Vanshul Saini,&nbsp;Roshni Malviya,&nbsp;Rutuja Kshirsagar,&nbsp;Mahesh Kashyap,&nbsp;Abhay T. Sangamwar","doi":"10.1016/j.ejpb.2025.114809","DOIUrl":"10.1016/j.ejpb.2025.114809","url":null,"abstract":"<div><div>Mebendazole (MBZ), a brick dust molecule with poor aqueous solubility tends to precipitate at intestinal pH, impeding its gastrointestinal absorption. Moreover, the amorphous MBZ tends to recrystallize in conventional amorphous solid dispersion (ASD) during long-term storage, reducing its physical stability and solubility. The present investigation explored amorphous salt solid dispersion (ASSD), an emerging approach combining salt formation with ASD, where the counterion and polymer are crucial in forming a stable supersaturated system. The maximal supersaturation holding capacity of hydroxypropyl methylcellulose acetate succinate polymer and its potential to lower the melting endotherm of MBZ demonstrate its suitability for ASSD preparation, via acid-base reaction between HCl and MBZ. P-XRD and DSC confirmed the amorphization of MBZ in ASSD, exhibiting a higher T_g and improved physical stability. ¹H NMR and FTIR spectroscopy confirmed the protonation of nitrogen during salt formation, with stronger salt-polymer interactions that stabilized the amorphous MBZ in ASSD, preventing recrystallization for 12 months, compared to ASD. Additionally, ASSD exhibited synergistic enhancement in solubility (7.58-folds) and dissolution (11.17-folds) of MBZ, which translated into <em>in vivo</em> studies, demonstrating 2.99-folds increase in C_max. Hence, findings revealed ASSD as a potential approach for augmenting the biopharmaceutical performance of MBZ over ASD.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114809"},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648897","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, characterization, and optimization of folate-chitosan surface-modified PLGA-decorated mesoporous silica nanoparticles for effective delivery of leflunomide for the management of rheumatoid arthritis","authors":"Walaa A. El-Dakroury ,&nbsp;Fatma Sa’eed El-Tokhy ,&nbsp;Gihan F. Asaad ,&nbsp;Marwa E. Shabana ,&nbsp;Kareem H. Elsyed ,&nbsp;Haya A. Elshafei ,&nbsp;Mostafa M. Mohamed ,&nbsp;Mohamed A. Radwan ,&nbsp;Abdelrahman R. Said","doi":"10.1016/j.ejpb.2025.114808","DOIUrl":"10.1016/j.ejpb.2025.114808","url":null,"abstract":"<div><div>Folate-chitosan surface modification of PLGA-decorated mesoporous silica nanoparticles (FC-PLGA-MSNs) was implemented to improve the delivery of leflunomide (LEF) for the management of rheumatoid arthritis (RA). These nanoparticles were designed to address LEF’s poor bioavailability and side effects, such as hepatotoxicity and gastrointestinal distress, by enhancing oral delivery and targetability to inflamed joints. Various MSNs were prepared and optimized with different levels of pH and silica precursor (TEOS). The optimized MSNs exhibited a size of 94.2 ± 3.3 nm, a zeta potential of −50.2 ± 4.5 mV, and a yield of 2.401 ± 0.17gm. Optimized MSNs were loaded with LEF with entrapment efficiency of 79.25 ± 3.84 %, subsequently coated with PLGA, and surface modified with folate-chitosan, producing FC-LEF-PLGA-MSNs demonstrating a nanometric size range and sustained drug release. The therapeutic efficacy of the FC-LEF-PLGA-MSNs was evaluated in a rat model of RA, showing significant antirheumatic effects compared to free and marketed LEF. Oral administration of the nanoparticles after RA induction significantly reduced joint swelling and histopathological damage. Additionally, the FC-LEF-PLGA-MSNs suppressed inflammatory cytokine levels, including TNF-α and IL-6, by 52.86 % and 55.12 %, respectively. These results demonstrate that FC-LEF-PLGA-MSNs provide an effective and safer alternative to free LEF for RA treatment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114808"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616917","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}