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Critical Reviews™ in Therapeutic Drug Carrier Systems

Impact factor: 3.174

ISSN Print: 0743-4863
ISSN Online: 2162-660X

Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v19.i2.30
20 pages

Glycosylated Cationic Liposomes for Cell-Selective Gene Delivery

Mitsuru Hashida
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Fumiyoshi Yamashita
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Koyo Nishida
School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8131, Japan
Junzo Nakamura
School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8131, Japan

ABSTRACT

Cationic liposomes have been considered as a potential nonviral vector for gene delivery because they possess low immunogenicity, unlike viral vectors. The gene transfer efficiency of cationic liposomes is lower than that of viral vectors, but recent advances have shown that it is possible to enhance the gene expression levels ofcationic liposomes. The main problem with cationic liposomes seems to be the lack of organ or cell selectivity because the lung has the highest level of gene expression after intravenous injection. Applying cell-specific targeting technology to liposomes would improve in vivo gene delivery and reduce any unexpected side effects. Both liver parenchymal and non-parenchymal cells exclusively express large numbers of high-affinity asialoglycoprotein and mannose receptors, respectively. Receptor-mediated gene delivery systems are able to introduce foreign DNA into specific cell types in vivo. However, we have confirmed that not only the nature of the ligands grafted to carriers but also the overall physicochemical properties of the complexes need to be optimized for effective cell-selective targeting of plasmid DNA. In this article, we attempt to evaluate a gene delivery system based on the physicochemical properties of plasmid DNA/glycosylated cationic complexes.