共 21 条
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.
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页码:2120 / 2128
页数:9