期刊
JOURNAL OF CONTROLLED RELEASE
卷 146, 期 1, 页码 106-117出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2010.05.030
关键词
Non-viral vector; Dendrimer conjugate; alpha-Cyclodextrin; Lactose; Hepatocyte
资金
- Japan Society for the Promotion of Science [14572158]
- Grants-in-Aid for Scientific Research [14572158] Funding Source: KAKEN
The purpose of this study is to evaluate in vitro and in vivo gene delivery efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2) conjugates with a-cyclodextrin (alpha-CDE (G2)) bearing lactose (Lac-alpha-CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel hepatocyte-selective carrier in hepatocytes. Lac-alpha-CDE (DSL 2.6) was found to have much higher gene transfer activity than dendrimer, alpha-CDE, Lac-alpha-CDE (DSL 1.2, 4.6, 6.2 and 10.2) and lactosylated dendrimer (Lac-dendrimer, DSL 2.4) in HepG2 cells, which are dependent on the expression of cell-surface asialoglycoprotein receptor (ASGP-R), reflecting the cellular association of the plasmid DNA (pDNA) complexes. The physicochemical properties of pDNA complex with Lac-alpha-CDE (DSL 2.6) were almost comparable to that with alpha-CDE. Lac-alpha-CDE (DSL 2.6) provided negligible cytotoxicity up to a charge ratio of 150 in HepG2 cells. Lac-alpha-CDE (DSL 2.6) provided gene transfer activity higher than jetPEI (TM)-Hepatocyte to hepatocytes with much less changes of blood chemistry values 12 h after intravenous administration in mice. These results suggest the potential use of Lac-alpha-CDE (DSL 2.6) as a non-viral vector for gene delivery toward hepatocytes. (C) 2010 Elsevier B.V. All rights reserved.
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