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Liposome–polyethylenimine complexes for enhanced DNA and siRNA delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
8725 603 2010 9 PDF Available
Title
Liposome–polyethylenimine complexes for enhanced DNA and siRNA delivery
Abstract

The efficient delivery of nucleic acids into cells is critical for successful gene therapy or gene knockdown. Polyethylenimines (PEIs) are positively charged polymers which complex and deliver DNA for gene transfection or small interfering RNAs (siRNAs) for the induction of RNA interference (RNAi), and mediate their endosomal release. Likewise, various liposomes act as transfection reagents, with some lipids showing increased endocytosis and influencing endosomal escape. This study combines the favourable properties of PEI and lipid systems for DNA and siRNA delivery. Various lipids and lipid combinations, which cover a broad range of physicochemical properties and form optimal liposomes, are assessed. By addition of the liposomes to pre-formed polyplexes, based on the low molecular weight PEI F25-LMW, we establish liposome–PEI complexes (lipopolyplexes) and characterise them in comparison to their ‘parent’ polyplexes and liposomes regarding size, shape and zeta-potential. Furthermore, while the lipidation of polyplexes generally decreases their toxicity, our studies on DNA transfection and siRNA-mediated knockdown also establish certain lipopolyplexes based on rigid, negatively charged lipids as particularly efficient vehicles for nucleic acid delivery, further improving DNA transfection. The analysis of their mechanism and kinetics of cellular uptake confirms that the biological properties of lipopolyplexes are mainly determined by the liposome shell. We conclude that certain lipopolyplexes show improved biological properties over PEI complexes, thus representing potentially attractive non-viral vectors for gene therapy and RNAi.

Keywords
Liposomes; Gene delivery; RNAi; siRNAs; Polyethylenimine; Lipid coating
First Page Preview
Liposome–polyethylenimine complexes for enhanced DNA and siRNA delivery
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 26, September 2010, Pages 6892–6900
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering