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Biodegradable nanoparticles composed of dendrigraft poly-l-lysine for gene delivery


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Title: Biodegradable nanoparticles composed of dendrigraft poly-l-lysine for gene delivery
Authors: Kodama, Yukinobu / Nakamura, Tadahiro / Kurosaki, Tomoaki / Egashira, Kanoko / Mine, Toyoharu / Nakagawa, Hiroo / Muro, Takahiro / Kitahara, Takashi / Higuchi, Norihide / Sasaki, Hitoshi
Issue Date: Aug-2014
Publisher: Elsevier
Citation: European Journal of Pharmaceutics and Biopharmaceutics, 87(3), pp.472-479; 2014
Abstract: We developed novel gene vectors composed of dendrigraft poly-l-lysine (DGL). The transgene expression efficiency of the pDNA/DGL complexes (DGL complexes) was markedly higher than that of the control pDNA/poly-l-lysine complex. However, the DGL complexes caused cytotoxicity and erythrocyte agglutination at high doses. Therefore, γ-polyglutamic acid (γ-PGA), which is a biodegradable anionic polymer, was added to the DGL complexes to decrease their toxicity. The resultant ternary complexes (DGL/γ-PGA complexes) were shown to be stable nanoparticles, and those with γ-PGA to pDNA charge ratios of >8 had anionic surface charges. The transgene expression efficiency of the DGL/γ-PGA complexes was similar to that of the DGL complexes; however, they exhibited lower cytotoxicity and did not induce erythrocyte agglutination at high doses. After being intravenously administered to mice, the DGL6 complex demonstrated high transfection efficiency in the liver, lungs, and spleen, whereas the DGL6/γ-PGA8 complex only displayed high transfection efficiency in the spleen. Future studies should examine the utility of DGL and DGL/γ-PGA complexes for clinical gene therapy.
Keywords: Biodegradable / Dendrigraft poly-l-lysine / Gene delivery / Nanoparticle / Ternary complex / γ-Polyglutamic acid
URI: http://hdl.handle.net/10069/34974
ISSN: 09396411
DOI: 10.1016/j.ejpb.2014.04.013
Rights: © 2014 Elsevier B.V. / NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in European Journal of Pharmaceutics and Biopharmaceutics, 87, 3, (2014)
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34974

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