title: Biocompatible complex coated with glycosaminoglycan for gene delivery.
abstract: The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with dendrigraft poly-l-lysine (DGL) and biodegradable glycosaminoglycan for effective and secure gene delivery. High gene expression of pDNA/DGL complex was confirmed with slight cytotoxicity and erythrocyte agglutination. Anionic ternary complexes of 55.4-223.8 nm were formed by the addition of a glycosaminoglycan such as chondroitin sulfate A (CS-A), chondroitin sulfate B (CS-B), chondroitin sulfate C (CS-C) or hyaluronic acid (HA). Using the cell line B16-F10, most of the ternary complexes showed only weak gene expression and little cytotoxicity, although the pDNA/DGL/CS-A complexes maintained a certain level of gene expression. In particular, the pDNA/DGL/CS-A8 complexes showed significantly higher gene expression than pDNA/DGL complexes in the presence of fetal bovine serum. Gene expression from the pDNA/DGL/CS-A8 complex was inhibited by a high concentration of CS-A and endocytosis inhibitors. After intravenous administration of the pDNA/DGL/CS-A8 complex and the pDNA/DGL complex into ddY mice, high gene expression was observed in the reticuloendothelial systems, the pDNA/DGL/CS-A complex is expected to be useful for gene therapy.
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.|b Department of Clinical Pharmacokinetics, Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Iwanaga
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Muro
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Sato
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.affiliation: a Department of Hospital Pharmacy , Nagasaki University Hospital , Nagasaki , Japan.|b Department of Clinical Pharmacokinetics, Graduate School of Biomedical Sciences , Nagasaki University , Nagasaki , Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006025:Glycosaminoglycans; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000628:therapy; D051379:Mice; D008856:Microscopy, Fluorescence; D013154:Spleen / Q000378:metabolism
chemical_list: D020099:Coated Materials, Biocompatible; D006025:Glycosaminoglycans
keywords: Dendrigraft poly-l-lysine; biodegradable; chondroitin sulfate; drug delivery; gene therapy; glycosaminoglycan; hyaluronic acid