Preparation and characterization of novel dendrimer-based gene delivery systems

Huang Rongqin; Liu Shuhuan; Han Liang; Jiang Chen

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Preparation and characterization of novel dendrimer-based gene delivery systems

Huang Rongqin #,Liu Shuhuan,Han Liang,Jiang Chen *

School of Pharmacy, Fudan University

*Correspondence author

#Submitted by

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Funding: none

Opened online:11 January 2011

Accepted by: none

Citation: Huang Rongqin,Liu Shuhuan,Han Liang.Preparation and characterization of novel dendrimer-based gene delivery systems[OL]. [11 January 2011] http://en.paper.edu.cn/en_releasepaper/content/4402823

Purpose: Dendrimers have attracted great interests in the field of gene delivery due to their synthetic controllability and excellent gene transfection efficiency. The aim of this work is to develop a novel dendrimer-based gene delivery system. Methods and Results: Dendrigraft poly-L-lysines (DGLs) were evaluated as a novel gene vector for the first time. Derivatives of DGLs (generation 2 and 3) with different extents of PEGylation were successfully synthesized and used to compact pDNA as complexes. The result of gel retardation assay showed that pDNA could be effectively packed by all the vectors at a DGLs to pDNA weight ratio greater than 2. An increase in the PEGylation extent of vectors resulted in a decrease in the incorporation efficiency and cytotoxicity of complexes in 293 cells, which also decreased the zeta potential a little but did not affect the mean diameter of complexes. Higher generation of DGLs could mediate higher gene transfection in vitro. Confocal microscopy and cellular uptake inhibition studies demonstrated that caveolae-mediated process and macropinocytosis were involved in the cellular uptake of DGLs-based complexes. Conclusion: All the results indicate that proper PEGylated DGLs could mediate efficient gene tranfection, showing their potential as an alternate biodegradable vector in the field of nonviral gene delivery.

Keywords:Pharmaceutics; dendrigraft poly-L-lysines; PEGylation; nonviral gene delivery; intracellular trafficking

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