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

被引：62

作者：

Kodama, Yukinobu ^{[1
]}

Nakamura, Tadahiro ^{[1
]}

Kurosaki, Tomoaki ^{[1
]}

Egashira, Kanoko ^{[1
]}

Mine, Toyoharu ^{[1
]}

Nakagawa, Hiroo ^{[1
]}

Muro, Takahiro ^{[1
]}

Kitahara, Takashi ^{[1
]}

Higuchi, Norihide ^{[1
]}

Sasaki, Hitoshi ^{[1
]}

机构：

[1] Nagasaki Univ Hosp, Dept Hosp Pharm, Nagasaki 8528501, Japan

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2014年 / 87卷 / 03期

关键词：

Dendrigraft poly-L-lysine; Biodegradable; Gene delivery; gamma-Polyglutamic acid; Nanoparticle; Ternary complex; D-GLUTAMIC ACID; IN-VITRO; DENDRITIC POLY(L-LYSINE); CAPSULAR ANTIGEN; DNA; DENDRIMERS; COMPLEXES; PROTEINS; GLYCOSAMINOGLYCANS; CAVEOLAE;

D O I：

10.1016/j.ejpb.2014.04.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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, gamma-polyglutamic acid (gamma-PGA), which is a biodegradable anionic polymer, was added to the DGL complexes to decrease their toxicity. The resultant ternary complexes (DGL/gamma-PGA complexes) were shown to be stable nanoparticles, and those with gamma-PGA to pDNA charge ratios of >8 had anionic surface charges. The transgene expression efficiency of the DGL/gamma-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/gamma-PGA8 complex only displayed high transfection efficiency in the spleen. Future studies should examine the utility of DGL and DGL/gamma-PGA complexes for clinical gene therapy. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：472 / 479

页数：8

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