The effect of conditions of preparation on the size and encapsulation properties of PLGA-mPEG nanoparticles of cisplatin was investigated. A modified double emulsion method was applied for the preparation of PLGAmPEG nanoparticles of cisplatin, based on the partial or complete replacement of the water of the inner aqueous phase of the emulsion by dimethyl formamide(dmf) or the addition of cisplatin in the form of a complex with poly(glutamic acid). These modifications resulted in significant improvement of cisplatin loading in the PLGA-mPEG nanoparticles. Increased cisplatin loading and encapsulation efficiency were obtained when a relatively low dmf/water ratio, low dmf volume (when pure dmf formed the inner polar phase), or a high drug/polymer ratio were applied. A reduction of average size of nanoparticles was observed with decreasing the amount of PLGA-mPEG added in the formulation or increasing sonication time. The only factor that had a significant effect on size distribution was the sonication time, with the size P.I. being decreased with increasing sonication time. Prolonged sonication, however, decreased cisplatin loading and encapsulation efficiency. From the four lyoprotectant sugars tested (glucose, lactose, mannitol, and trehalose), only mannitol could prevent nanoparticle aggregation upon lyophilization. When appropriate amounts of an effective lyoprotectant were added in nanoparticles before lyophilization, drug loading of the nanoparticles was not affected by nanoparticle lyophilization.