School of Pharmaceutical Sciences, School of Life Science, Jiangxi Science and Technology Normal University, Nanchang 330013, China.
School of Pharmaceutical Sciences, School of Life Science, Jiangxi Science and Technology Normal University, Nanchang 330013, China.
Int J Biol Macromol. 2019 Oct 15;139:377-386. doi: 10.1016/j.ijbiomac.2019.07.224. Epub 2019 Aug 1.
Cancer chemotherapy and the patient's life will be more convenient if oral administration of anti-cancer drugs can be achieved. The feasibility of folate-targeted Pluronic F127/polylactic acid (FA-F127-PLA) polymersomes as the oral delivery carriers of paclitaxel (PTX) has been explored in this study. PTX loaded in FA-F127-PLA and PLA-F127-PLA polymersomes showed biphasic release behaviors in simulated gastric and intestinal fluids. PTX loaded in FA-F127-PLA polymersomes exhibited higher cytotoxicity and cellular uptake than PTX loaded in PLA-F127-PLA polymersomes. In vivo pharmacokinetic studies in rats showed that oral PTX loaded in FA-F127-PLA polymersomes had a higher bioavailability than oral PTX loaded in PLA-F127-PLA polymersomes. D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) was also added to the FA-F127-PLA polymersomes as an optimization agent. Compared with PTX-loaded FA-F127-PLA polymersome, PTX-loaded FA-F127-PLA/TPGS mixed polymersomes showed even better cytotoxic ability, more cellular uptake and higher bioavailability. The above results indicate that FA-F127-PLA and FA-F127-PLA/TPGS mixed polymersomes could be good candidates for the oral delivery carrier of anti-cancer drugs.
如果可以实现抗癌药物的口服给药，癌症化疗和患者的生活将更加便利。本研究探索了叶酸靶向的 Pluronic F127/聚乳酸（FA-F127-PLA）聚合物囊泡作为紫杉醇（PTX）口服递药载体的可行性。在模拟胃液和肠液中，载有 PTX 的 FA-F127-PLA 和 PLA-F127-PLA 聚合物囊泡表现出两相释放行为。载有 FA-F127-PLA 聚合物囊泡的 PTX 比载有 PLA-F127-PLA 聚合物囊泡的 PTX 表现出更高的细胞毒性和细胞摄取。在大鼠体内药代动力学研究中，口服载有 FA-F127-PLA 聚合物囊泡的 PTX 比口服载有 PLA-F127-PLA 聚合物囊泡的 PTX 具有更高的生物利用度。D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS 或维生素 E TPGS）也被添加到 FA-F127-PLA 聚合物囊泡中作为优化剂。与载有 PTX 的 FA-F127-PLA 聚合物囊泡相比，载有 PTX 的 FA-F127-PLA/TPGS 混合聚合物囊泡表现出更好的细胞毒性、更高的细胞摄取和更高的生物利用度。上述结果表明，FA-F127-PLA 和 FA-F127-PLA/TPGS 混合聚合物囊泡可能是抗癌药物口服递药载体的良好候选物。
