Antifungal efficacy of miltefosine in alginate nanocarrier in the treatment of aspergillosis

• Grant number: 18/03708-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2018
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Kelly Ishida
• Grantee: Thayná Lopes Barreto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Aspergillus spp. are responsible for causing opportunistic diseases in immunocompromised patients leading to high mortality rates. Among the species found dispersed worldwide in the air, Aspergillus fumigatus is the most common, being identified in 90% of the cases. Despite the effectiveness of triazole agents, the number of resistant isolates to this class of antifungals has increased in recent years due to continued use in the clinical practice and in the agriculture. The high mortality rate and the increase of resistant strains make it important to search for alternatives and treatment strategies. Miltefosine (MFS), an akylphosphocholine compound, is licensed for the treatment of leishmaniasis and breast cancer in several countries; In addition, previous studies have demonstrated that MFS has broad spectrum of action on pathogenic fungi and fungicidal effect, but it has high toxicity. Our research group has been working on the development of a formulation of MFS in an alginate nanocarrier system for controlled and sustained release of the drug, resulting in the reduction of toxicity and maintenance of antifungal activity in vitro and in vivo against Candida and Cryptococcus. It is worth noting that this formulation was previously standardized and the technology recently protected by the National Institute of Industrial Property (INPI, Brazil) under number BR 10 2017 018011 5 (request date: 08/23/2017). Thus, the main objective of the present work is to evaluate the antifungal efficacy of MFS in an alginate nanocarrier system on A. fumigatus and A. flavus using experimental models in vitro and in vivo. (AU)

Scientific publications

(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)

BARRETO, THAYNA LOPES; ROSSATO, LUANA; DUARTE DE FREITAS, ALINE LUIZA; MEIS, JACQUES F.; LOPES, LUCIANA BIAGINI; COLOMBO, ARNALDO LOPES; ISHIDA, KELLY. Miltefosine as an alternative strategy in the treatment of the emerging fungus Candida auris. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 56, n. 2, AUG 2020. (17/19374-9, 18/13877-1, 18/03708-8, 17/15226-5, 17/02203-7, 17/19095-2)

BARRETO, THAYNA L.; LOPES, LUCIANA B.; MELO, ANALY S. A.; ISHIDA, KELLY. In vivo synergism of free miltefosine or in alginate-based nanocarrier combined with voriconazole on aspergillosis. FUTURE MICROBIOLOGY, v. 16, n. 15, OCT 2021. (17/19374-9, 15/07993-0, 18/03708-8, 18/13877-1)

Academic Publications

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

BARRETO, Thayná Lopes. Antifungal efficacy in vitro e in vivo of miltefosine encapsulated in alginate nanoparticles on treatment of aspergilosis and systemic candidiasis.. 2020. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.