In this study, poly(D,L-lactide-co-glycolide) (PLGA)-chitosan particles were investigated as an effective delivery system for small interfering RNA (siRNA) by emulsification diffusion method. The type, molecular weight and concentration of chitosan, PLGA type as well as centrifugation and freeze-drying process were amongst the investigated variables. PLGA-chitosan particles obtained were positively charged with particle size between 0.4-1 m depending on type, molecular weight and concentration of chitosan as well as type of PLGA. A better siRNA loading capacity was observed when a higher degree of 'uncapped end groups' were used. The addition of trehalose has also been shown to stabilize these particles from severe aggregation induced by freeze-drying. It was found that physical properties of PLGA-chitosan particles and their siRNA binding capacity were highly influenced by certain preparation parameters. The desired positive charge of submicron size range PLGA-chitosan particles could therefore be obtained by adjusting and optimizing these preparative and formulation parameters.