期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 375, 期 1-2, 页码 133-139出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2009.03.033
关键词
Gene therapy; Non-viral vector; Targeting gene delivery; Mannosylated chitosan-graft-PEI; Antigen presenting cell
资金
- Korea Science and Engineering Foundation (KOSEF)
- Korea government (MEST) [ROA-2008-000-20024-0]
- National Instrumentation Center for Environmental Management (NICEM)
Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic genes. Among non-viral vectors, chitosans have been proposed as alternative, biocompatible cationic polymers for non-viral gene delivery. However, the low transfection efficiency and low specificity of chitosan needs to be addressed prior to clinical application. In this study, mannosylated chitosan-graft-polyethylenimine (Man-CHI-g-PEI) copolymer was prepared by thiourea reaction between the isothiocyanate group of mannopyranosylphenylisothiocyanate and the amine groups of chitosan-graft-PEI (CHI-g-PEI) for targeting into antigen presenting cells (APCs) having mannose receptors. The composition and molecular weight were characterized using H-1 NMR and GPC, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. Man-CHI-g-PEI showed good DNA binding ability and high protection of DNA from nuclease attack and had low cytotoxicity compared with PEI 25K. The transfection efficiency of Man-CHI-g-PEI/DNA complexes into the Raw 264.7 macrophage cell line, which has mannose receptors, was higher than CHI-g-PEI itself as well as PEI 25K, indicating Man-CHI-g-PEI can be used as an APCs' targeting gene delivery carrier. (C) 2009 Elsevier B.V. All rights reserved.
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