Folate-conjugated pluronic/polylactic acid polymersomes for oral delivery of paclitaxel
Folate-conjugated pluronic/polylactic acid polymersomes for oral delivery of paclitaxel
复制标题
用于紫杉醇口服递送的叶酸缀合的普朗尼克/聚乳酸聚合物囊泡。
DOI：
10.1016/j.ijbiomac.2019.07.224
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发表时间：
2019-10-15
影响因子：
8.2
通讯作者：
Xiong, Xiang Yuan
中科院分区：
文献类型：
--
作者：
Pan, Xiao Qian;Gong, Yan Chun;Xiong, Xiang Yuan
如果能够实现抗癌药物的口服给药，将给癌症化疗和患者的生活带来更大的方便。探讨叶酸靶向的Pluronic F127/聚乳酸（FA-F127-PLA）聚合物囊泡作为紫杉醇（PTX）口服给药载体的可行性。PTX在FA-F127-PLA和PLA-F127-PLA聚合物囊泡中在模拟胃液和肠液中呈双相释放。装载在FA-F127-PLA聚合物囊泡中的PTX表现出比装载在PLA-F127-PLA聚合物囊泡中的PTX更高的细胞毒性和细胞摄取。大鼠体内药代动力学研究表明，FA-F127-PLA聚合物囊泡中的口服PTX比PLA-F127-PLA聚合物囊泡中的口服PTX具有更高的生物利用度。还将D-α-生育酚聚（乙二醇）1000琥珀酸酯（TPGS或维生素E TPGS）作为优化剂添加到FA-F127-PLA聚合物囊泡中。与载PTX的FA-F127-PLA聚合物囊泡相比，载PTX的FA-F127-PLA/TPGS混合聚合物囊泡具有更好的细胞毒活性、更高的细胞摄取率和更高的生物利用度。上述结果表明FA-F127-PLA和FA-F127-PLA/TPGS混合聚合物囊泡是一种良好的抗癌药物口服给药载体。(C)2019 Elsevier B. V.版权所有。
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-a-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. (C) 2019 Elsevier B.V. All rights reserved.