Poly(ethylenimine) conjugated bioreducible dendrimer for efficient gene delivery

JOURNAL OF CONTROLLED RELEASE

卷:220

Article

Nam, Kihoon¹  Jung, Simhyun¹  Nam, Joung-Pyo¹  Kim, Sung Wan¹ 

[1] Univ Utah, Ctr Controlled Chem Delivery, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA

关键词: Biodegradation;    Cytotoxicity;    Gene expression;    Poly(ethylenimine);    Dendrimer;   

DOI  :  10.1016/j.jconrel.2015.11.005

来源: Elsevier

【 摘 要 】

Branched poly(ethylenimine) (PEI) 25 kDa is an efficient gene delivery vector with outstanding gene condensation ability and great endosome escape activity. However, it also induces higher cytotoxicity. Transfection efficiency and toxicity of PEI are highly dependent upon their molecular weight and structure. We developed a bioreducible poly(ethylenimine) (PEI (-s-s-)) derived from low molecular weight PEI (1.8 kDa) for efficient gene delivery. Bioreducible core molecule is expected to increase molecular weight and reduce the cytotoxicity of the copolymer. PEI (-s-s-) polyplexes showed higher transfection efficiency and lower cytotoxicity compared to branched PEI 25 kDa, Lipofectamine (R) 2000 and, FuGENE (R) 6. In addition, PEI (-s-s-) derivative (16 kDa) formed stable polyplexes with a zeta-potential value of + 34 mV and polyplex size of 61 nm. PEI (-s-s-) derivative (16 kDa) showed excellent transfection efficiency: 3.6 times higher than branched PEI 25 kDa in HeLa cells and 7.4 times higher than Lipofectamine (R) 2000 in H9C2 cell. The derivatives also showed lower cytotoxicity compared with Lipofectamine (R) 2000 and PEI 25 kDa in various cell types. In addition, newly synthesized PEI (-s-s-) derivatives have high reproducibility. (C) 2015 Elsevier B.V. All rights reserved.

【 授权许可】

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