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Gene delivery using dimethyldidodecylammonium bromide-coated PLGA nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
9130 617 2010 9 PDF Available
Title
Gene delivery using dimethyldidodecylammonium bromide-coated PLGA nanoparticles
Abstract

In this present work we describe a poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulation for intracellular delivery of plasmid DNA. This formulation was developed to encapsulate DNA within PLGA nanoparticles that combined salting out and emulsion–evaporation processes. This process reduced the requirement for sonication which can induce degradation of the DNA. A monodispersed nanoparticle population with a mean diameter of approximately 240 nm was produced, entrapping a model plasmid DNA in both supercoiled and open circular structures. To induce endosomal escape of the nanoparticles, a superficial cationic charge was introduced using positively charged surfactants cetyl trimethylammonium bromide (CTAB) and dimethyldidodecylammonium bromide (DMAB), which resulted in elevated zeta potentials. As expected, both cationic coatings reduced cell viability, but at equivalent positive zeta potentials, the DMAB coated nanoparticles induced significantly less cytotoxicity than those coated with CTAB. Fluorescence and transmission electron microscopy demonstrated that the DMAB coated cationic nanoparticles were able to evade the endosomal lumen and localise in the cytosol of treated cells. Consequently, DMAB coated PLGA nanoparticles loaded with a GFP reporter plasmid exhibited significant improvements in transfection efficiencies with comparison to non-modified particles, highlighting their functional usefulness. These nanoparticles may be useful in delivery of gene therapies to targeted cells.

Keywords
Gene therapy; Nanoparticle; Drug delivery; Polyglycolic acid; Polylactic acid; Dimethyldidodecylammonium bromide
First Page Preview
Gene delivery using dimethyldidodecylammonium bromide-coated PLGA nanoparticles
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 14, May 2010, Pages 4214–4222
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering