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Splenic Delivery System of pDNA through Complexes Electrostatically Constructed with Protamine and Chondroitin Sulfate

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Title: Splenic Delivery System of pDNA through Complexes Electrostatically Constructed with Protamine and Chondroitin Sulfate
Authors: Kodama, Yukinobu / Nishigaki, Waka / Nakamura, Tadahiro / Fumoto, Shintaro / Nishida, Koyo / Kurosaki, Tomoaki / Nakagawa, Hiroo / Kitahara, Takashi / Muro, Takahiro / Sasaki, Hitoshi
Issue Date: 1-Mar-2018
Publisher: 日本薬学会 / Pharmaceutical Society of Japan
Citation: Biological and Pharmaceutical Bulletin, 41(3), pp.342-349; 2018
Abstract: We developed and optimized a novel gene delivery vector constructed electrostatically with an anionic biological component and a cationic biological component. Cationic binary complexes of plasmid DNA (pDNA) with novo-protamine sulfate as a medical product (PRT complexes) demonstrated high gene expression with minimal cytotoxicity, likely related with its total cationic charge. Subsequently, anionic compounds were added to the PRT complexes to form ternary complexes with neutral or anionic charges. Among the anionic compounds examined, chondroitin sulfate sodium (CS) as a medical product encapsulated the PRT complexes to produce stable ternary complexes (CS complexes) at charge ratios of ?4 with pDNA. CS complexes exhibited high gene expression without cytotoxicity in mouse melanoma cell line, B16-F10 cells, in vitro. An inhibition study with endocytosis inhibitors suggested that PRT complexes were mainly taken up by caveolae-mediated endocytosis, and CS complexes were mainly taken up by clathrin-mediated endocytosis in B16-F10 cells. We found that CS complexes including pDNA encoding Oplophorus gracilirostris luciferase induced selective gene expression in the spleen after intravenous administration into ddY male mice. Thus, we successfully constructed useful gene vectors with biological components as medical products.
Keywords: Chondroitin sulfate sodium / Gene delivery / Medical product / Plasmid DNA / Protamine sulfate
URI: http://hdl.handle.net/10069/38244
ISSN: 09186158
DOI: 10.1248/bpb.b17-00667
Rights: © 2018 The Pharmaceutical Society of Japan.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/38244

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