Long-term drug release is needed to treat ocular diseases, especially in the posterior region where the retina is located. Dexamethasone, an anti-inflammation drug, was encapsulated in biocompatible and biodegradable polylactic acid/polylactic-co-glycolic acid (PLA, PLGA 90:10, PLGA 50:50) nanoparticles prepared using the solvent evaporation method. The surface of the nanoparticles was modified with didodecyldimethylammonium bromide (DDAB), a cationic surfactant, to increase the residence time in the vitreous, by contacting the nanoparticles with various surfactant solutions (PVA, DDAB-1%, PVA-DDAB-0.5%, PVA-DDAB-1%). Those modified using DDAB-1% solution exhibit the highest positive zeta potential (52.7±9.3 mV) and the smallest particle size (329±44 nm). Dexamethasone released into a buffer release media (45°C, 100 rpm) from nanoparticles with higher lactic acid content (PLA and PLGA 90:10) showed zero- order release profile up to 48 days with 30-70% accumulative release. On the other hand, the DDAB release profiles show that after 6-12 days, the cationic surfactant was detached from the surface of the nanoparticles.