Encapsulation of doxorubicin in chitosan-alginate nanoparticles improves its stability and cytotoxicity in resistant lymphoma L5178 MDR cells

The present study evaluated the impact of doxorubicin encapsulation in chitosan-alginate nanoparticles on its stability, cytotoxic potential in multidrug resistant lymphoma cells (L5178 MDR1) and toxicity in H9c2 cardioblasts. The results indicated that the encapsulation stabilized the drug against degradation due to its inner location in nanoparticles as suggested by thermogravimetric and X-ray diffraction analyses. Further, the encapsulated doxorubicin was significantly more cytotoxic to L5178 MDR1 cells than free doxorubicin. A flow cytometry assay revealed that the encapsulation did not improve the drug uptake by L5178 MDR1 cells, but increased the amount of doxorubicin that remains intracellularly 12 h after discontinuation of the treatment. The treatment of cardioblasts with subcytotoxic concentrations of doxorubicin showed that the free drug impacted negatively the glutathione antioxidant system by reducing the ratio between the reduced and the oxidized form of glutathione (GSH/GSSG), whereas the encapsulated did not cause statistically significant changes in GSH/GSSG levels. The observed protective effects were probably the result of antioxidant properties of the drug delivery system, since the empty nanoparticles improved the GSH/GSSG ratio themselves. Thus, the chitosan-alginate nanoparticles could be considered advantageous delivery system because of improved drug stability, increased cytotoxicity in resistant L5178 MDR1 cells and possible reduction of cardiotoxic effects.