Inhibition of Growth and Lung Metastasis of Breast Cancer by pH-Responsive Methotrexate/Curcumin-Loaded Chitosan-Stabilized Nanoemulsions

Chemotherapeutic agents are widely used to combat breast cancer. However, due to their non-selective biodistribution, their usage is associated with severe adverse effects on healthy tissues. In this study, a chitosan-stabilized nanoemulsion (CSNE) was prepared for the codelivery of curcumin (CUR) and methotrexate (MTX). The mean diameter and polydispersity index of CUR-MTX-CSNEs were 194.63 ± 6.7 nm and 0.27 ± 0.06, respectively. Modifying the nanoemulsion surface with chitosan decreased the drug release at pH 7.4 compared to pH 5.8. The MTT test demonstrated that CUR-MTX-CSNEs were more successful in reducing the cell viability of 4T1 cells than both bare formulation and free drugs. Moreover, compared to the free drug-treated group, a 2.6 times reduction of the relative tumor volume was witnessed in CUR-MTX-CSNEs-receiving mice. Histopathological studies confirmed a more substantial inhibitory effect on tumor growth and pulmonary metastasis of developed nanostructures than free CUR/MTX. While there was not any noticeable toxicity in the vital organs of CUR-MTX-CSNEs-receiving mice, free drugs resulted in severe toxicity in the liver, kidney, lung, and spleen. Overall, the pH-dependent drug release, improved anti-tumor activity, and reduced organ toxicity suggest that CUR-MTX-CSNE may be promising in breast cancer therapy.