El-Dakroury Walaa A, El-Tokhy Fatma Sa'eed, Asaad Gihan F, Shabana Marwa E, Elsyed Kareem H, Elshafei Haya A, Mohamed Mostafa M, Radwan Mohamed A, Said Abdelrahman R
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
Eur J Pharm Biopharm. 2025 Sep;214:114808. doi: 10.1016/j.ejpb.2025.114808. Epub 2025 Jul 9.
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.
对聚乳酸-羟基乙酸共聚物（PLGA）修饰的介孔二氧化硅纳米粒子（FC-PLGA-MSNs）进行叶酸-壳聚糖表面修饰，以改善来氟米特（LEF）的递送，用于类风湿性关节炎（RA）的治疗。这些纳米粒子旨在通过增强口服递送和对炎症关节的靶向性，解决LEF生物利用度差以及肝毒性和胃肠道不适等副作用问题。制备了各种介孔二氧化硅纳米粒子，并通过不同的pH值和二氧化硅前驱体（正硅酸乙酯）水平进行优化。优化后的介孔二氧化硅纳米粒子尺寸为94.2±3.3nm，zeta电位为-50.2±4.5mV，产率为2.401±0.17gm。用LEF负载优化后的介孔二氧化硅纳米粒子，包封率为79.25±3.84%，随后用PLGA包衣，并用叶酸-壳聚糖进行表面修饰，制得的FC-LEF-PLGA-MSNs呈现纳米尺寸范围并具有药物缓释性能。在RA大鼠模型中评估了FC-LEF-PLGA-MSNs的治疗效果，与游离和市售的LEF相比，显示出显著的抗风湿作用。RA诱导后口服纳米粒子可显著减轻关节肿胀和组织病理学损伤。此外，FC-LEF-PLGA-MSNs分别将炎症细胞因子水平，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）抑制了52.86%和55.12%。这些结果表明，FC-LEF-PLGA-MSNs为RA治疗提供了一种比游离LEF更有效、更安全的替代方案。
