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Multilayered polyplexes with the endosomal buffering polycation in the core and the cell uptake-favorable polycation in the outer layer for enhanced gene delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
8555 597 2010 7 PDF Available
Title
Multilayered polyplexes with the endosomal buffering polycation in the core and the cell uptake-favorable polycation in the outer layer for enhanced gene delivery
Abstract

In the present study, quaternary polyplexes were prepared by sequential addition of polycations (polyethylenimine (PEI) or poly (N-(8-aminooctyl)-acrylamide) (P8Am)) for loading pDNA into the core polyplexes and poly (acrylic acid) (PAA) for reversing charges to deposit additional polycation (PEI or P8Am) layer. It was found the cytotoxicity and cellular uptake expression of PEI core polyplexes could be improved by coating a cell uptake-favorable P8Am layer. Conversely, P8Am could not facilitate endosomal release through the proposed proton sponge effect so the PEI core was required for the P8Am-coated quaternary polyplexes to ensure efficient transfection. Consequently, an efficient and safe non-viral gene vehicle was constructed by layer-by-layer deposition, using alternate polyanion and polycation with required functionalities to overcome the obstacles met in the process of transfection. Maximum transfection activity with minimal toxicity was observed when the quaternary polyplex of pDNA/PEI/PAA/P8Am was prepared at a weight ratio of 1/1.5/3/5. Conversely, the same composition in different position such as the cell-favorable P8Am core was externally deposited with the endosome lytic moiety, PEI showed high toxicity and low efficiency. This indicates the pDNA/PEI/PAA/P8Am sequence for a quaternary polyplex is as important as the functional polymer selection for designing safe and reliable gene delivery vehicles. We demonstrate here that gene delivery efficiency may be improved by increasing the uptake level and the endosomal buffering release through an additional layer of cell uptake-favorable polycations associated with the core polycations possessing endosomal release ability.

Keywords
Gene therapy; Gene vehicle; Polyelectrolyte multilayer; Polycation
First Page Preview
Multilayered polyplexes with the endosomal buffering polycation in the core and the cell uptake-favorable polycation in the outer layer for enhanced gene delivery
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 35, December 2010, Pages 9366–9372
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering