Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge

被引:374
作者
Yamamoto, Y
Nagasaki, Y
Kato, Y
Sugiyama, Y
Kataoka, K
机构
[1] Univ Tokyo, Grad Sch Engn, Dept Mat Sci, Bunkyo Ku, Tokyo 1138656, Japan
[2] Tokyo Univ Sci, Dept Mat Sci, Noda, Chiba 2788510, Japan
[3] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
关键词
poly(ethylene glycol); poly(D; L-lactide); block copolymer micelles; peptidyl ligand; biodistribution;
D O I
10.1016/S0168-3659(01)00451-5
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Reactive polymeric micelles consisting of an alpha -acetal-poly(ethylene glycol) -poly(D,L-lactide) block copolymer (acetal-PEG-PDLLA) with a narrow size distribution were prepared in this study to conjugate small peptidyl ligands, tyrosine (Tyr) and tyrosyl-glutamic acid (Tyr-Glu), through reductive amination after converting the a-acetal group to an aldehyde group, allowing modulation of the surface charge of the micelles from neutral (Tyr-) to anionic (Tyr-Glu-). Both of these micelles showed a significantly long circulating time in the blood compartment with 25% of injected dose still circulating even at 24 h. Further, an appreciably lowered uptake into the liver and spleen was demonstrated for the anionic Tyr-Glu-conjugated PEG-PDLLA micelle compared with a neutral Tyr-conjugated micelle, suggesting a substantial role of the slight anionic charge on the micelle surface in avoiding non-specific organ uptake. Stability of the micelle form in the blood compartment was directly observed for the Tyr-PEG-PDLLA micelle by a gel filtration assay of a plasma sample collected from the micelle-injected mice at 24 h. These results demonstrated that a surface-modulated PEG-PDLLA micelle with a suitable size and a narrowly distributed nature has promising potential as a long-circulating carrier system with desirable biocompatibility and biofunctionality. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:27 / 38
页数:12
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