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

• Main Authors: Loanda Aparecida Cabral Rudnik, Paulo Vitor Farago, Jane Manfron Budel, Amanda Lyra, Fernanda Malaquias Barboza, Traudi Klein, Carla Cristine Kanunfre, Jessica Mendes Nadal, Matheus Coelho Bandéca, Vijayasankar Raman, Andressa Novatski, Alessandro Dourado Loguércio, Sandra Maria Warumby Zanin
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Molecules
• Subjects: Calu-3 cell line; cancer chemotherapy; drug resistance; poly(<i>ε</i>-caprolactone); poly(ethylene glycol)
• Online Access: https://www.mdpi.com/1420-3049/25/8/1913

<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.