Polyethylenimine coated plasmid DNA–surfactant complexes as potential gene delivery systems

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Nanometer scaled particles have been prepared from strong association between plasmid DNA (pcDNA3-FLAG-p53) and oppositely charged surfactants. Although these particles present suitable properties for gene delivery purposes, their cytotoxicity could compromise their use in gene therapy applications. To ensure biocompatibility of this potential gene delivery system, the nanoparticles were coated with polyethylenimine (PEI) with various molar ratios of PEI nitrogen to plasmid DNA phosphate groups. This led to a drastic increase in the cell viability of the particles, and in addition particle characteristics such as size, surface charge and loading efficiency, have also been enhanced as a result of the PEI coating process. The dissolution or swelling/deswelling behaviour displayed by these particulate vehicles could be tailored and monitored in time, to promote the controlled and sustained release of plasmid DNA. Moreover, we show that both the surfactant alkyl chain length and the ratio of nitrogen to phosphate groups are important parameters for controlling the plasmid DNA release. Overall, the developed plasmid DNA carriers have the potential as a new nanoplatform to be further explored for advances in the gene therapy field.