Galactosylated low molecular weight chitosan as DNA carrier for hepatocyte-targeting

被引：125

作者：

Gao, SY ^{[1
]}

Chen, JN ^{[1
]}

Xu, XR ^{[1
]}

Ding, Z ^{[1
]}

Yang, YH ^{[1
]}

Hua, ZC ^{[1
]}

Zhang, JF ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Dept Biochem, Nanjing 210093, Peoples R China

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2003年 / 255卷 / 1-2期

基金：

中国国家自然科学基金;

关键词：

chitosan; non-viral gene delivery; galactosylated chitosan; liver-specificity;

D O I：

10.1016/S0378-5173(03)00082-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Chitosan has the potential for DNA complexation and is useful as a non-viral vector for gene delivery. Highly purified low molecular weight chitosan (LMWC) was prepared. Lactobionic acid (LA) bearing galactose group as coupled with LMWC for liver-specificity. A series of galactoslated-LMWC (gal-LMWC) samples covering a range of galactose group contents were prepared. The chitosan/DNA complexes were obtained using a complex coacervation process. Gal-LMWCs were used to transfer pSV-beta-galactosidase reporter gene into human hepatocellular carcinoma cell (HepG2). L-02. SMMC-7721, and human cervix adenocarcinoma cell line (HeLa) cell lines in vitro. Transfection efficiency of gal-LMWCs was evaluated by beta-galactosidase assay and compared with those of lipofectin, calcium phosphate (CaP). high molecular weigh chitosan (HMWC) and LMWC. Gal-LMWC/DNA complex shows a very, efficient cell selective transfection to hepatocyte. The transfection efficiency of gal-LMWCs increased with the improvement of the galactosylation degree. Cytotoxicity of gal-LMWC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltentrazolium bromide (MTT) assay and the results show that the modified chitosan has relatively low cytotoxicity. giving the evidence that the modified chitosan vector has the potential to be used as a safe gene-delivery system. (C) 2003 Elsevier Science B.V. All rights reserved.

引用

页码：57 / 68

页数：12

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