Synthesis, characterization and drug loading property of Monomethoxy-Poly(ethylene glycol)-Poly(ε-caprolactone)-Poly(D, L-lactide) (MPEG-PCLA) copolymers

被引:48
作者
Chu, BingYang [1 ,2 ,3 ,4 ,5 ]
Zhang, Lan [2 ]
Qu, Ying [3 ,4 ,5 ]
Chen, XiaoXin [2 ]
Peng, JinRong [1 ]
Huang, YiXing [1 ]
Qian, ZhiYong [2 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Orthopaed Surg, 109 Xueyuan Rd, Wenzhou 325027, Peoples R China
[2] Guangdong Zhongsheng Pharmaceut Co Ltd, R&D Ctr New Prod, Dongguan 523325, Peoples R China
[3] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China
[4] Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Peoples R China
[5] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China
关键词
BLOCK-COPOLYMER; HYDROLYTIC DEGRADATION; POLYMERIC MICELLES; IN-VITRO; EPSILON-CAPROLACTONE; CREMOPHOR-FREE; GENEXOL-PM; PACLITAXEL; PHARMACOKINETICS; DISPOSITION;
D O I
10.1038/srep34069
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Amphiphilic block copolymers have attracted a great deal of attention in drug delivery systems. In this work, a series of monomethoxy-poly (ethylene glycol)-poly (epsilon-caprolactone-co-D, L-lactide) (MPEG-PCLA) copolymers with variable composition of poly (epsilon-caprolactone) (PCL) and poly (D, L-lactide) (PDLLA) were prepared via ring-opening copolymerization of epsilon-CL and D, L-LA in the presence of MPEG and stannous octoate. The structure and molecular weight were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The crystallinity, hydrophilicity, thermal stability and hydrolytic degradation behavior were investigated in detail, respectively. The results showed that the prepared amphiphilic MPEG-PCLA copolymers have adjustable properties by altering the composition of PCLA, which make it convenient for clinical applications. Besides, the drug loading properties were also studied. Docetaxel (DTX) could be entrapped in MPEG-PCLA micelles with high loading capacity and encapsulation efficiency. And all lyophilized DTX-loaded MPEG-PCLA micelles except MPEG-PCL micelles were readily re-dissolved in normal saline at 25 degrees C. In addition, DTX-loaded MPEG-PCLA micelles showed a slightly enhanced antitumor activity compared with free DTX. Furthermore, DTX micelles exhibited a slower and sustained release behavior in vitro, and higher DTX concentration and longer retention time in vivo. The results suggested that the MPEG-PCLA copolymer with the adjustable ratio of PCL to PDLLA may be a promising drug delivery carrier for DTX.
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页数:15
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