Production, physicochemical characterization, and anticancer activity of methotrexate-loaded phytic acid-chitosan nanoparticles on HT-29 human colon adenocarcinoma cells

Abstract

Methotrexate-loaded phytic acid-chitosan nanoparticles were synthesized by ionic gelation assisted by high-intensity sonication. The nanoparticles were characterized by particle size, polydispersity index, zeta potential (ZP) and encapsulation efficiency. Their physical stability was evaluated at 4 °C and 40 °C, whereas the in-vitro methotrexate release was assessed at pH 7.4. The data were heuristically fit to first-order, Higuchi, Peppas-Sahlin and Korsmeyer-Peppas models of release kinetics. Anticancer activity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay on HT-29 human colon adenocarcinoma cells. Physicochemical analysis showed that the nanoparticles presented positive ZP values, sizes less than <300 nm and low polydispersity, except for systems formed with low amplitude sonication. The nanoparticles exhibited an adequate physical stability and a capability to modify methotrexate release by a non-Fickian mechanism, resulting in a more pronounced cytotoxic effect than the free drug on HT-29 human colon adenocarcinoma cells.