Abstract

DTX-loaded folate targeted micelles (DTX/FA-PEG-HEP-CA-TOC) were prepared using a dialysis method and the impact of various processing variables were evaluated on micelle properties. In vitro cytotoxicity and in vivo pharmacokinetics of the optimized formulation were evaluated.

DTX/FA-PEG-HEP-CA-TOC exhibited average particle size of 90–185 nm with high entrapment efficiency (53–93%) and pH-dependent drug release behavior. DTX/FA-PEG-HEP-CA-TOC micelles exhibited higher toxicity against SKOV3 cells than DTX/HEP-CA-TOC micelles and free DTX. Significant increase in the T_1/2 β, AUC and MRT and decrease in V_d as well as CL values was observed in DTX/FA-PEG-HEP-CA-TOC micelle treated group compared to free DTX treated group.

摘要

使用透析方法制备负载 DTX 的叶酸靶向胶束 (DTX/FA-PEG-HEP-CA-TOC)，并评估各种加工变量对胶束特性的影响。评估了优化制剂的体外细胞毒性和体内药代动力学。

DTX/FA-PEG-HEP-CA-TOC 的平均粒径为 90-185 nm，具有高包封率 (53-93%) 和 pH 依赖性药物释放行为。DTX/FA-PEG-HEP-CA-TOC 胶束对 SKOV3 细胞的毒性高于 DTX/HEP-CA-TOC 胶束和游离 DTX。与游离 DTX 处理组相比，在 DTX/FA-PEG-HEP-CA-TOC 胶束处理组中观察到T _1/2 β、AUC 和 MRT显着增加以及V _d和 CL 值降低。