Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells

Abstract

<i>Background</i>: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. <i>Methods</i>: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. <i>Results</i>: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (-33 to -41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. <i>Conclusions</i>: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.