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The ionic gelation technique allows us to obtain nanoparticles able to function as carriers for hydrophobic anticancer drugs, such as 5-fluoruracil (5-FU). In this study, reticulated chitosan- docosahexaenoic acid (Chi-DHAr) nanoparticles were synthesized by using a chemical reaction between amine groups of chitosan (Chi) and carboxylic acids of docosahexaenoic acid (DHA) and the presence of a link between Chi and DHA was confirmed by FT-IR, while the size and morphology of the obtained Chi-DHAr nanoparticles was evaluated with dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Drug-loading content (DLC) and drug-loading efficiency (DLE) of 5-FU in Chi-DHAr nanoparticles were 33.74 ± 0.19% and 7.9 ± 0.26%, respectively, while in the non-functionalized nanoparticles (Chir + 5FU), DLC, and DLE were in the ranges of 23.73 ± 0.14%, 5.62%, and 0.23%, respectively. The in vitro release profile, performed in phosphate buffer saline (PBS, pH 7.4) at 37 °C, indicated that the synthetized Chi-DHAr nanoparticles provided a sustained release of 5-FU. Based on the obtained regression coefficient value (R 2 ), the first order kinetic model provided the best fit for both Chir and Chi-DHAr nanoparticles. Finally, cytotoxicity studies of chitosan, 5-FU, Chir, Chir + 5-FU, Chi-DHAr, and Chi-DHAr + 5-FU nanoparticles were conducted. Overall, Chi-DHAr nanoparticles proved to be much more biocompatible than Chir nanoparticles while retaining the ability to release the drug with high efficiency, especially towards specific types of cancerous cells.

journal of functional biomaterials

Controlled Release of 5-FU from Chi–DHA Nanoparticles Synthetized with Ionic Gelation Technique: Evaluation of Release Profile Kinetics and Cytotoxicity Effect