Targeted delivery of paclitaxel using folate-conjugated heparin-poly(β-benzyl-L-aspartate) self-assembled nanoparticles

被引:20
作者
Li, Li [1 ]
Kim, Jun Ki
Huh, Kang Moo [1 ]
Lee, Yong-kyu [2 ]
Kim, So Yeon [3 ]
机构
[1] Chungnam Natl Univ, Dept Polymer Sci & Engn, Taejon 305764, South Korea
[2] Chungju Natl Univ, Coll Adv Sci & Technol, Dept Chem & Biol Engn, Chungju 380702, South Korea
[3] Chungnam Natl Univ, Dept Chem Engn Educ, Coll Educ, Taejon 305764, South Korea
基金
新加坡国家研究基金会;
关键词
Nanoparticle; Drug delivery; Active targeting; Paclitaxel; Heparin; DRUG; HEPARIN; MICELLES;
D O I
10.1016/j.carbpol.2011.10.030
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
A self-assembled nanoparticulate system composed of a folate-conjugated heparin-poly(beta-benzyl-L-aspartate) (HP) amphiphilic copolymer was proposed for targeted delivery of the antineoplastic drug paclitaxel (PTX). PTX was incorporated into three types of heparin-based nanoparticles, including HP, folate-conjugated HP (FHP), and folate-polyethylene glycol (PEG)-conjugated HP (FPHP), using a simple dialysis method. The PTX-loaded nanoparticles were then characterized according to particle size (140-190 nm) and size distribution, drug-loading content and efficiency, and in vitro release behavior. In the cellular uptake study using KB cells positive for the folate-receptor (FR), FHP and FPHP nanoparticles showed a much higher cellular uptake than did unconjugated HP nanoparticles. Specifically, when the PEG spacer was inserted between the folate ligand and heparin backbone, FPHP nanoparticles had a greater cellular uptake than did FHP nanoparticles. The in vitro cytotoxicity of PTX-loaded HP, FHP, and FPHP nanoparticles was studied in KB cells and FR-negative A549 cells. Compared with the cytotoxicity in A549 cells, PTX-loaded FHP and FPHP nanoparticles exhibited more potent cytotoxicity in KB cells than did PTX-loaded HP nanoparticles and free-PTX, suggesting that the presence of folate enhanced intracellular uptake via FR-mediated endocytosis. In addition, FPHP nanoparticles exhibited much greater cytotoxicity in KB cells than did FHP nanoparticles. These results suggest that PTX-loaded folate-conjugated HP nanoparticles are a potentially useful delivery system for cancer cells positive for the folate-receptor. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2120 / 2128
页数:9
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