Biodegradable triblock copolymer of PLGA-PEG-PLGA enhances gene transfection efficiency

Purpose. A tri-block copolymer of PLGA-PEG-PLGA was used as an excipient to enhance the gene transfection efficiency of various cationic polymeric carriers. Methods. Luciferase plasmid DNA was complexed with polyethylenimine for gene transfection. Various concentrations of PLGA-PEG-PLGA copolymer up to 0.5% were added in the transfection medium to explore whether the copolymer increased the level of gene expression. Pluronic F68 was used as a control. Various polyplexes and different cell lines were used to verify the effect of the triblock copolymer on gene transfection. The cellular uptake extent of radiolabeled plasmid was quantitatively determined as a function of PLGA-PEG-PLGA concentration. Results. PLGA-PEG-PLGA copolymer significantly enhanced gene transfection efficiency at a concentration as low as 0.25% (w/v), which was more effective than Pluronic F68 at the same concentration range. The additive effect of the triblock copolymer in the transfection medium was clearly observed for various cationic polyplexes and cell lines, although the gene expression extents largely depended on polymers and cell lines used. Five- to 10-fold increment of gene transfection levels were attained in the presence of the PLGA-PEG-PLGA tri-block copolymer. The enhanced gene transfection efficiency was attributed to the increased cellular uptake of PEI/DNA complexes in the presence of the PLGA-PEG-PLGA tri-block copolymer. Conclusions. Biodegradable PLGA-PEG-PLGA tri-block copolymer that facilitates the endocytic process can be used as a novel additive in non-viral gene transfection.