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Surface modified DL-lactide/glycolide coptolymer (PLGA) nanospheres with chitosan (CS) were prepared by the emulsion solvent diffusion (ESD) method for improving siRNA delivery.The particle size of PLGA NS was about 300tam.Encapsulation efficiency of siRNA increased by coformulating the cationic complexing agent with siRNA (DOTAP).By coating with CS, PLGA NS exhibited high encapsulation efficiency.CS coated PLGA NS revealed a positive charge on zeta potential, while PLGA NS being negatively charged.The siRNA uptake studies and confocal leaser scanning microscopy (CLSM) observation indicated that the CS-PLGA NS loaded with siRNA were effectively taken up by the cells more than uncoated PLGA NS, In addition, the cellular uptake efficiency of the different siRNA preparations was compared on the level of protein expression.The gene silencing efficiency of CS-PLGA NS was higher and prolonged than that of uncoated PLGA NS.This result might be caused by higher cellular uptake ability of CS-PLGA NS due to electrostatic interaction.It was concluded that surface modified PLGA nanospheres with CS containing siRNA could serve as an effective siRNA delivery system.