2008 Volume 16 Pages 21-29
Recently, many nonviral vectors modified with cationic lipids, cationic polymers, etc. for facilitating gene therapy have been reported. However, those nonviral vectors with cationic materials require improved stability, longer duration of gene expression, and reduced cytotoxicity. We found that nucleic acid, which was not dispersed in the organic solvent, could be dispersed by forming a complex with cationic lipid. Using this phenomenon, polynucleic acids for gene therapy (plasmid DNA, antisense oligonucleotide, small interfering RNA, etc.) can be encapsulated into the matrix of the biodegradable polymer particles which is poly-lactic-glycolic acid (PLGA) with the emulsion solvent diffusion method. The advantages of this preparation method are its simple process and avoidance of an ultrasonication process for submicronization of particles. Furthermore, by modification of nanoparticulate surface by chitosan or TweenR 80 (polysorbate 80), the nanospheres show better cellular uptake and different gene therapeutic effects compared with conventional vectors due to their improved adherence to cells and sustained release of polynucleic acid in the cells. In conclusion, surface modified PLGA nanospheres can possibly be applied in nonviral vectors for gene therapy.