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Open AccessFeature PaperArticle

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

1
Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil
2
Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná, 81020-430 Curitiba, Brazil
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Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa, 84030-900 Ponta Grossa, Brazil
4
Postgraduate Program in Dentistry, Ceuma University, 65065-470 São Luís, Brazil
5
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Maria Carla Marcotullio
Molecules 2020, 25(8), 1913; https://doi.org/10.3390/molecules25081913
Received: 6 March 2020 / Revised: 11 April 2020 / Accepted: 17 April 2020 / Published: 21 April 2020
Background: 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. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: 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. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer. View Full-Text
Keywords: Calu-3 cell line; cancer chemotherapy; drug resistance; poly(ε-caprolactone); poly(ethylene glycol) Calu-3 cell line; cancer chemotherapy; drug resistance; poly(ε-caprolactone); poly(ethylene glycol)
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Rudnik, L.A.C.; Farago, P.V.; Manfron Budel, J.; Lyra, A.; Barboza, F.M.; Klein, T.; Kanunfre, C.C.; Nadal, J.M.; Bandéca, M.C.; Raman, V.; Novatski, A.; Loguércio, A.D.; Zanin, S.M.W. Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells. Molecules 2020, 25, 1913.

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