Caiyun Deng1, Chang Xu2, Xiaomin Zhang2, J U Yao2, Yingxin Zhang2, B O Yu2, Robert J Lee3, Chengjun Jiang4. 1. Department of Chemical and Biological Engineering, Zhejiang University of Science & Technology, Hangzhou, Zhejiang, P.R. China. 2. Hangzhou Push-Kang Biotechnology Co., Ltd., Hangzhou, Zhejiang, P.R. China. 3. Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A. jcj312@163.com lee.1339@osu.edu. 4. Department of Chemical and Biological Engineering, Zhejiang University of Science & Technology, Hangzhou, Zhejiang, P.R. China jcj312@163.com lee.1339@osu.edu.
Abstract
BACKGROUND/AIM: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX. Copyright
BACKGROUND/AIM: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION:mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX. Copyright