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CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

Efficient Gene Transfer into Macrophages and Dendritic Cells by in Vivo Gene Delivery with Mannosylated Lipoplex via the Intraperitoneal Route

Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan

In this study, we developed an antigen-presenting cell (APC)-selective intraperitoneal (i.p.) gene delivery system with mannosylated cationic liposomes (Man-liposomes)/plasmid DNA complex (Man-lipoplex). An in vitro study using cultured peritoneal macrophages demonstrated that Man-liposomes could transfect luciferase-encoding plasmid DNA (pCMV-Luc) more efficiently than cationic liposomes via a mannose receptor-mediated mechanism. In vivo gene transfection studies revealed that Man-lipoplex showed a higher gene expression in the liver, spleen, peritoneal exuded cells, and mesenteric lymph nodes than cationic liposomes/plasmid DNA complex (lipoplex) or naked pCMV-Luc after i.p. administration, and this gene expression lasted for at least 24 h. The transfection activity of Man-lipoplex after i.p. administration was significantly higher than that after i.v. gene delivery with the Man-liposomes we developed previously, indicating that gene delivery via the i.p. route seems to be an efficient approach for in vivo gene delivery to APCs. Furthermore, it was demonstrated that Man-lipoplex could enhance gene expression in both F4/80⁺ and CD11c⁺ cells in the spleen. These results show that gene delivery with Man-liposomes via the i.p. route could be an effective approach for APC-selective gene transfection.

Address correspondence to: Dr. Mitsuru Hashida, Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. E-mail: hashidam{at}pharm.kyoto-u.ac.jp