Abstract：
Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and in vitro and ex vivo drug release. An in vivo study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. The in vitro and ex vivo drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.
摘要：
恩曲他滨（FTC）是BCSI类药物，用于预防艾滋病毒。药物的高溶解度是严重肝毒性和乳酸性酸中毒的主要原因。本研究的重点是使用修饰的普鲁兰多糖制备FTC聚合物脂质体。改性普鲁兰是用胆固醇合成的，和琥珀酸酐在受控的化学环境中。通过光谱分析确定聚合物的形成。改变药物-聚合物比例（1:1、1:2和1:3），药物-聚合物复合物负载在大豆磷脂酰胆碱和胆固醇的囊泡系统中。评估制剂的药物包封，颗粒大小,表面形态,以及体外和离体药物释放。在每天口服给药后,对小鼠进行纯药物和最佳制剂的体内研究28天,以评价对肝脏和血液学参数的影响。对最好的制剂进一步进行肝细胞系的细胞毒性研究。光谱分析证实了改性普鲁兰的形成。所有制剂均显示在纳米囊泡中的高药物截留。体外和离体药物释放曲线描绘了药物的受控释放。在整个实验过程中,发现动物的血液学参数受到控制。对肝脏的比较组织病理学研究和对肝细胞系的细胞毒性研究表明，与纯药物相比，最佳制剂的安全性。因此,可以得出结论,FTC的聚合物脂质体可以是克服其局限性的有希望的递送模式。
