The main objectives of the present research were to determine the effects of different coating agents and techniques on different characteristics, and cellular uptake of a new antiproliferative drug - meloxicam - loaded PLGA nanoparticles, and to evaluate their safety and potential use as drug carriers for colon cancer treatment. For this purpose, nanoparticles with a mean diameter of 17820 tun were successfully prepared. Two different surface coating techniques the in situ coating technique and the surface adsorption method were used as coating processes with PEG 2000 and DMAB. A rate of 2.5 % DMAB-coated PLGA nanoparticles had an average size of 17750 tun with a zeta potential of approximately + 4.72 mV, while PEG-modified nanoparticles using the in situ coating technique had a smaller particle size and negative zeta potential. The cell viability assays demonstrated that the cytotoxicity of nanoparticles was significantly affected by the coating process and both of the modified formulations were found more potent than pure meloxicam.