PEG-poly(amino acid) Block Copolymer Micelles for Tunable Drug Release

被引:70
作者
Ponta, Andrei [1 ]
Bae, Younsoo [1 ]
机构
[1] Univ Kentucky, Coll Pharm, Lexington, KY 40536 USA
关键词
controlled drug delivery; functional block copolymers; pH-sensitive drug release; polymer micelles; tunable drug release; POLYMERIC MICELLES; ANTITUMOR-ACTIVITY; INTRACELLULAR TRAFFICKING; POLY(ETHYLENE GLYCOL); ANTICANCER DRUG; ADRIAMYCIN; DELIVERY; CARRIER; DESIGN; SYSTEM;
D O I
10.1007/s11095-010-0120-z
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37A degrees C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed < 50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 +/- 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.
引用
收藏
页码:2330 / 2342
页数:13
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