Malignant wound – The influence of oil components in flubendazole-loaded nanoemulsions in A549 lung cancer xenograft-bearing mice

• Published in: Journal of drug delivery science and technology Vol. 78; p. 103963
• Main Authors: Yukuyama, Megumi Nishitani, Guimaraes, Lara Mendes Ferreira, Segovia, Rafael Scheliga, Lameu, Claudiana, de Araujo, Gabriel Lima Barros, Löbenberg, Raimar, de Souza, Aline, Henostroza, Mirla Anali Bazán, Folchini, Beatriz Rabelo, Peroni, Camilla Midori, Miyagi, Mariana Yasue Saito, Oliveira, Isabela Fernandes, Alvarenga, José Fernando Rinaldi, Fiamoncini, Jarlei, Bou-Chacra, Nádia Araci
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-12-2022
• Subjects: d-phase emulsification; Flubendazole; Lung cancer; Malignant wound; Nanoemulsion; d-phase emulsification; Flubendazole; Lung cancer; Malignant wound; Nanoemulsion
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103963

Malignant wounds (MWs) affect up to 15% of advanced stage cancer patients, causing detrimental effects such as tissue deformity and extreme malodor, affecting the social and psychological quality of life of these patients. Although treating MW is mandatory to prevent infections and reduce wound healing time, this disease has often been overlooked by researchers. For the first time, we propose a new alternative MW treatment for oral administration using high-oil-content flubendazole (FLZ) loaded in nanoemulsions, prepared by the d-phase emulsification process. We performed in vivo tests on the A549 xenograft murine model and compared FLZ in suspension, drug-free nanoemulsion, FLZ-loaded nanoemulsion containing oil derived from linoleic acid, and FLZ-loaded nanoemulsion containing mixture of oils. Mice treated by gavage three times a week with FLZ in suspension, drug-free nanoemulsion, and FLZ-loaded nanoemulsion with mixed oil, presented MW emergence in 20–40% of the cases at different time intervals and extents. However, mice treated with FLZ-loaded nanoemulsion containing only the oil derived from linoleic acid presented MW emergence in 0% of cases, even after 80 days of treatment. Thus, we observed a positive synergy between the drug FLZ and the oil derived from linoleic acid in the treatment of MW. Discussions on the mechanism of action of this oil and the drug are intensively described in this article. We present such FLZ-loaded nanoemulsion as a promising prevention and treatment solution for greater patient compliance and lower adverse effects.
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•Malignant wound (MW) is one of the most complex and difficult disease to treat, but it is often undervalued.•Nanoemulsions were prepared by the d-Phase Emulsification Method at 25 ± 0.5 °C.•Oral administration of nanoemulsion loaded with flubendazole and linoleic acid-derived oil did not show the presence of MW.•The comparison between the different preparations showed distinct results in the percentage of occurrence and time of MW.