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

Author(s):Show less -

Yukuyama, Megumi Nishitani ; Ferreira Guimaraes, Lara Mendes ; Segovia, Rafael Scheliga ; Lameu, Claudiana ; Barros de Araujo, Gabriel Lima ; Lobenberg, Raimar ; de Souza, Aline ; Bazan Henostroza, Mirla Anali ; Folchini, Beatriz Rabelo ; Peroni, Camilla Midori ; Saito Miyagi, Mariana Yasue ; Oliveira, Isabela Fernandes ; Rinaldi Alvarenga, Jose Fernando ; Fiamoncini, Jarlei ; Bou-Chacra, Nadia Araci

• Document type: Journal article
• Source: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 78, p. 10-pg., 2022-11-12.

Abstract

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. (AU)

• FAPESP's process: 18/22713-2 - Study of Flubendazole repositioning for the treatment of lung cancer and MENINGOENCEFALITE employing oral lipid nanosystem
• Grantee: Megumi Nishitani Yukuyama
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/15981-0 - Repositioning study of flubendazol for the treatment of lung cancer and meningoencephalitis using oral lipid nanosystem
• Grantee: Megumi Nishitani Yukuyama
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/04998-2 - Nanocrystalline and amorphous solid dispersions formulations for improvement of antitumor therapies
• Grantee: Gabriel Lima Barros de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/19128-2 - Metastasis mechanisms of childhood tumors to bone marrow
• Grantee: Claudiana Lameu
• Support Opportunities: Research Grants - Young Investigators Grants