Abstract：
This study was designed to improve oral bioavailability of the methotrexate (MTX) by sustaining its release profile and integration into core-shell polymeric nanoparticles. The self-micellization and ionotropic gelation technique was employed which resulted into spherical shaped nanoparticles (181-417 nm) with encapsulation efficiency of 80.14% to 85.54%. Furthermore, Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry analyses were carried out to investigate physicochemical and thermal stability of the produced engineered core shell nanoparticles of the methotrexate. . Entrapment of drug in polymeric core was confirmed by X-ray diffraction analysis. In-vitro sustained release behavior of nanoparticles was observed at pH 6.8 for 48 h while low drug release was observed at pH 1.2 due to pH-responsive nature of Pluronic F127. Acute toxicity study confirmed safety and biocompatible profile of nanoparticles. MTX loaded polymeric nanoparticles ameliorated the pharmacokinetic profile (8 folds greater half-life, 6.26 folds higher AUC0-t and 3.48 folds higher mean residence time). In vivo study conducted in rat model depicted the improved therapeutic efficacy and healing of arthritis through MTX loaded polymeric nanoparticles, preferentially attributable to high accretion of MTX in the inflamed site. In conclusion, MTX loaded polymeric nanoparticles is an attractive drug delivery strategy for an effective management and treatment of rheumatoid arthritis.
摘要：
这项研究旨在通过维持甲氨蝶呤（MTX）的释放曲线并整合到核-壳聚合物纳米颗粒中来提高其口服生物利用度。采用自胶束化和离子凝胶化技术，得到球形纳米颗粒（181-417nm），包封率为80.14％至85.54％。此外，进行傅里叶变换红外光谱和差示扫描量热分析以研究所产生的甲氨蝶呤的工程核壳纳米颗粒的物理化学和热稳定性。.通过X射线衍射分析证实了药物在聚合物芯中的包封。在pH6.8下观察到纳米颗粒的体外持续释放行为48小时,而由于PluronicF127的pH响应性质,在pH1.2下观察到低药物释放。急性毒性研究证实了纳米颗粒的安全性和生物相容性。负载MTX的聚合物纳米颗粒改善了药代动力学特征（半衰期延长8倍，AUC0-t高出6.26倍，平均停留时间高出3.48倍）。在大鼠模型中进行的体内研究描绘了通过负载MTX的聚合物纳米颗粒改善的治疗功效和关节炎的愈合,优先归因于MTX在发炎部位的高积聚。总之,负载MTX的聚合物纳米颗粒是有效管理和治疗类风湿性关节炎的有吸引力的药物递送策略。
