Study of Flubendazole repositioning for the treatment of lung cancer and MENINGOENCEFALITE employing oral lipid nanosystem

• Grant number: 18/22713-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2019
• End date: January 31, 2023
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Nádia Araci Bou-Chacra
• Grantee: Megumi Nishitani Yukuyama
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 20/15981-0 - Repositioning study of flubendazol for the treatment of lung cancer and meningoencephalitis using oral lipid nanosystem, BE.EP.DR

Abstract

The growing demand for new drugs faces important barriers to be overcome. Such barriers are related to efficacy, safety, compliance with regulatory requirements and cost-effectiveness balance. Despite the progressive investment of companies in research, studies show that in the United States, only 0.1% of new drugs under development advance to clinical studies. Within these, only 10.0% are approved. In this context, there is an urgent need for more efficient alternatives for drug development, especially in the treatment of specific diseases such as neglected and different types of cancer. Drug repositioning accounts for about 30% of new drugs approved by the Food and Drug Administration (FDA) in recent years. This strategy has attracted increasing interest from governments, nongovernmental agencies, and academic researchers in identifying new roles for existing drugs. Flubendazole, a drug that acts mainly on microtubules, has potential use in different treatments such as lymphatic filariasis, meningoencephalitis, and in various types of cancer, in nanomolar concentrations. However, the low water solubility of this drug may significantly limit its oral bioavailability. This limitation can be overcome by employing nanostructured systems. The present project aims at the development of lipid-based nanosystem to target flubendazole into the lymphatic system, for treatment of neglected diseases and cancer after oral administration, overcoming the problem of bioavailability and first-pass hepatic metabolism.

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAMASHIRO, F. L.; YUKUYAMA, M. N.; VELASCO, M. V. R.; DE ARAUJO, G. L. B.; BOU-CHACRA, N. A.. Nanoemulsions containing plant oils: How do they influence hair treatment?. International Journal of Cosmetic Science, DEC 2020. (18/22713-2)

YUKUYAMA, MEGUMI NISHITANI; DE ARAUJO, GABRIEL LIMA BARROS; DE SOUZA, ALINE; LOBENBERG, RAIMAR; BARBOSA, EDUARDO JOSE; HENOSTROZA, MIRLA ANALI BAZAN; ROCHA, NATALY PAREDES DA; OLIVEIRA, ISABELA FERNANDES DE; FOLCHINI, BEATRIZ RABELO; PERONI, CAMILLA MIDORI; et al. Cancer treatment in the lymphatic system: A prospective targeting employing nanostructured systems. International Journal of Pharmaceutics, v. 587, SEP 25 2020. (18/22713-2)

GONCALVES, DEBORA DE SOUZA; YUKUYAMA, MEGUMI NISHITANI; SAITO MIYAGI, MARIANA YASUE; VIEIRA SILVA, TAMARA JULIANE; LAMEU, CLAUDIANA; BOU-CHACRA, NADIA ARACI; BARROS DE ARAUJO, GABRIEL LIMA. Revisiting Flubendazole Through Nanocrystal Technology: Statistical Design, Characterization and Its Potential Inhibitory Effect on Xenografted Lung Tumor Progression in Mice. JOURNAL OF CLUSTER SCIENCE, v. N/A, p. 12-pg., 2022-01-14. (15/19128-2, 19/04998-2, 18/22713-2)

YUKUYAMA, MEGUMI NISHITANI; ZUO, JIEYU; PARK, CHULHUN; YOUSEF, MALAZ; BAZAN HENOSTROZA, MIRLA ANALI; BARROS DE ARAUJO, GABRIEL LIMA; BOU-CHACRA, NADIA ARACI; LOBENBERG, RAIMAR. Biphasic dissolution combined with modified cylinder method-A new promising method for dissolution test in drug-loaded nanoemulsions. International Journal of Pharmaceutics, v. 632, p. 9-pg., 2023-01-06. (18/22713-2, 20/15981-0, 19/04998-2, 17/08332-3)

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; et al. Malignant wound-The influence of oil components in flubendazole-loaded nanoemulsions in A549 lung cancer xenograft-bearing mice. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 78, p. 10-pg., 2022-11-12. (18/22713-2, 20/15981-0, 19/04998-2, 15/19128-2)

YUKUYAMA, MEGUMI NISHITANI; ISHIDA, KELLY; BARROS DE ARAUJO, GABRIEL LIMA; SPADARI, CRISTINA DE CASTRO; DE SOUZA, ALINE; LOBENBERG, RAIMAR; BAZAN HENOSTROZA, MIRLA ANALI; FOLCHINI, BEATRIZ RABELO; PERONI, CAMILLA MIDORI; CAMASMIE PETERS, MARIA CHRISTINA; et al. y Rational design of oral flubendazole-loaded nanoemulsion for brain delivery in cryptococcosis. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 630, DEC 5 2021. (18/12149-2, 17/19374-9, 18/22713-2)

TAMASHIRO, F. L.; YUKUYAMA, M. N.; VELASCO, M. V. R.; DE ARAUJO, G. L. B.; BOU-CHACRA, N. A.. Nanoemulsions containing plant oils: How do they influence hair treatment?. International Journal of Cosmetic Science, v. 43, n. 2, p. 8-pg., 2020-12-13. (18/22713-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

YUKUYAMA, Megumi Nishitani. Repositioning study of flubendazole for treating lung cancer and meningoencephalitis using an oral lipid nanosystem. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.