Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Pharm Biopharm. 2013 May;84(1):63-71. doi: 10.1016/j.ejpb.2012.12.010. Epub 2013 Jan 5.
The purpose of this work was to improve the efficacy of triamcinolone acetonide (TA) in the treatment of endotoxin-induced uveitis (EIU) using a polymeric nanoparticulate drug delivery system. Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were prepared using a modified emulsification/solvent diffusion method. Processing factors affecting loading and size were also studied. After physicochemical studies including in vitro release, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy, in vivo studies were conducted using nanoparticles sized 195 nm with 3.16% drug loading. Inflammatory factors such as flare, cell, and fibrin were studied in rabbit's eye over 96 h period, using laser flare meter and slit lamp examination. Inflammatory mediators such as NO, PGE2, cell, and protein were measured quantitatively 36 h after intravitreal injection of endotoxin in aqueous humor, and the therapeutic effects were compared in different groups. Results indicated statistically significant differences between the effect of nanoparticles in the treatment of EIU compared to microparticles of TA and prednisolone acetate (PA). There were no significant differences between the effects of TA injection and TA nanoparticles. In conclusion, sustain release biodegradable TA nanoparticles are potential new topical treatment options which can provide better patient compliance.
本工作旨在通过使用聚合物纳米颗粒药物传递系统来提高曲安奈德（TA）治疗内毒素性葡萄膜炎（EIU）的疗效。使用改良的乳化/溶剂扩散法制备了聚（D，L-丙交酯-co-乙交酯）（PLGA）纳米颗粒。还研究了影响载药量和粒径的加工因素。进行了包括体外释放、X 射线粉末衍射、差示扫描量热法和扫描电子显微镜在内的理化研究后，使用载药量为 3.16%、粒径为 195nm 的纳米颗粒进行了体内研究。使用激光闪烁仪和裂隙灯检查，在 96 小时的时间内研究了兔子眼中的炎症因子，如闪光、细胞和纤维蛋白。在房水中注射内毒素 36 小时后，定量测量了 NO、PGE2、细胞和蛋白质等炎症介质，并比较了不同组的治疗效果。结果表明，与 TA 和醋酸泼尼松龙（PA）的微粒相比，纳米颗粒治疗 EIU 的效果具有统计学显著差异。TA 注射和 TA 纳米颗粒的效果之间没有显著差异。总之，缓释可生物降解的 TA 纳米颗粒是潜在的新型局部治疗选择，可以提高患者的顺应性。
