Receptor-mediated delivery of all trans-retinoic acid to hepatocyte using poly(L-lactic acid) nanoparticles coated with galactose-carrying polystyrene

被引:59
作者
Cho, CS
Cho, KY
Park, IK
Kim, SH
Sasagawa, T
Uchiyama, M
Akaike, T
机构
[1] Seoul Natl Univ, Sch Agr Biotechnol, Suwon 441744, South Korea
[2] Seoul Natl Univ, Sch Biol Resources & Mat Engn, Suwon 441744, South Korea
[3] Tokyo Inst Technol, Dept Biomol Engn, Yokohama, Kanagawa 226, Japan
关键词
all trans-retinoic acids; nanoparticles; hepatocyte-specific; receptor-mediated;
D O I
10.1016/S0168-3659(01)00390-X
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
All trans-retinoic acid (RA)-loaded poly(L-lactic acid) (PLA) nanoparticles coated with galactose-carrying polymer, as hepatocyte-specific targeting material using galactose ligands as recognition signals to asialoglycoprotein receptors were prepared by the diafiltration method. Effects of released RA from its loaded nanoparticles on morphology and DNA synthesis of hepatocytes were studied. Receptor-mediated endocytosis of the nanoparticles was checked by fluorescence and confocal laser microscopy. It was found that the shapes of most hepatocytes attached onto polystyrene dish precoated with collagen solution were flat and spreading at low concentration of RA for the RA-loaded nanoparticles, whereas their shapes were round at even low concentration of RA when RA was mixed with the nanoparticles, From the fluorescence and confocal laser microscopic studies, it was suggested that the nanoparticles coated with galactose-carrying polymers were internalized by the hepatocytes through the receptor-mediated mechanism. The RA-loaded nanoparticles were more potent stimulators of hepatocyte DNA synthesis than the free RA system in the presence of epidermal growth factor (EGF) owing to the controlled release of RA from the RA-loaded nanoparticles. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:7 / 15
页数:9
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