Deng Caiyun, Xu Chang, Zhang Xiaomin, Yao J U, Zhang Yingxin, Yu B O, Lee Robert J, Jiang Chengjun
Department of Chemical and Biological Engineering, Zhejiang University of Science & Technology, Hangzhou, Zhejiang, P.R. China.
Hangzhou Push-Kang Biotechnology Co., Ltd., Hangzhou, Zhejiang, P.R. China.
Anticancer Res. 2018 Jan;38(1):219-225. doi: 10.21873/anticanres.12211.
BACKGROUND/AIM: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable.
Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide)-9-fluorenylmethoxycarbonyl-L-phenylalanine (mPEG-PDLLA-Phe(Fmoc)) was synthesized through a classical esterification reaction. Paclitaxel-loaded mPEG-PDLLA-Phe(Fmoc) micelles (PTX-PheMs) were prepared by the self-assembly method. Composition, structure and physicochemical properties were characterized. Pharmacokinetics were evaluated in rats. Therapeutic effect was evaluated in tumor-bearing mice. Safety profile was assessed by a hemolysis assay and an acute-toxicity study.
The average size of PTX-PheMs was about 45 nm. The hemolysis and acute-toxicity tests confirmed its biocompatibility and safety. The pharmacokinetics and therapeutic effect experiments demonstrated its long circulation property and superior antitumor effect.
mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX.
背景/目的：聚合物胶束是有前景的紫杉醇递送载体。胶束制剂的稳定性需要进一步提高。
通过经典酯化反应合成甲氧基聚（乙二醇）-嵌段-聚（D，L-丙交酯）-9-芴甲氧羰基-L-苯丙氨酸（mPEG-PDLLA-Phe(Fmoc)）。采用自组装法制备载紫杉醇的mPEG-PDLLA-Phe(Fmoc)胶束（PTX-PheMs）。对其组成、结构和理化性质进行了表征。在大鼠中评估了药代动力学。在荷瘤小鼠中评估了治疗效果。通过溶血试验和急性毒性研究评估了安全性。
PTX-PheMs的平均粒径约为45nm。溶血和急性毒性试验证实了其生物相容性和安全性。药代动力学和治疗效果实验证明了其长循环特性和优异的抗肿瘤效果。
mPEG-PDLLA-Phe(Fmoc)胶束是一种用于疏水性药物（如PTX）的生物相容性良好且有效的药物递送系统。
