ABSTRACT Self‐assembled nanoparticles prepared from amphiphilic chitosan/oleic acid (Ch/OA) have shown antibacterial activity and potential application as a carrier for hydrophobic anticancer drugs. In this study, a low molecular weight chitosan was modified with oleic acid obtaining a degree of substitution (DS) of 12%. The critical aggregation concentration (CAC) of the Ch/OA polymer obtained (0.025 mg mL −1 ) is lower in comparison with some systems of chitosan‐fatty acids. The self‐assembled Ch/OA nanoparticle size was optimized by changing polymer concentration, solvent, method, and time of homogenization to obtain particles with sizes around 300 nm and positive zeta potential. The drug loading about 7 μg mL −1 and encapsulation efficiency of 75.8 ± 3.6% for Celecoxib was affected by the drug concentration. In vitro release behavior performed in (PBS, pH 7.4) and MES buffer (pH 6) indicated a pH‐dependent drug release behavior. The self‐assembled systems show stability during 4 weeks after the encapsulation of the hydrophobic drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44472.