Platform for antifungal development in a nanostructured lipid system aiming at efficacy and safety in alternative animal models

• Grant number: 17/06658-9
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2018
• Effective date (End): January 05, 2021
• Field of knowledge: Health Sciences - Pharmacy
• Principal researcher: Maria José Soares Mendes Giannini
• Grantee: Junya de Lacorte Singulani
• Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 16/16212-5 - Natural proteopeptides from the Brazilian fauna, flora and microbiota as potential models for the rational development of new drugs of therapeutic use: isolation, structure elucidation, chemical synthesis and functional activity assays, AP.BTA.TEM
• Associated scholarship(s): 19/07938-0 - Determining the role of 14-3-3 protein in regulating intracellular growth of the human pathogen Cryptococcus, BE.EP.PD

Abstract

More than a billion people worldwide are estimated to suffer from some fungal disease and 1.5 to 2 million people die each year from a fungal infection, surpassing deaths from malaria or tuberculosis. Among these are those caused by Cryptococcus sp., Paracoccidioides sp. and Histoplasma capsulatum that are associated with high rates of morbidity and mortality. Treatment of these mycoses is by the combination of amphotericin B and azoles, with high toxicity and resistance rates. Although major advances have been made in the past decade, drug development has hardly evolved. Thus, the urgency to obtain new antifungal drugs stimulates the search for antimicrobial peptides. Additionally, the incorporation of these in nanostructured lipid systems becomes an important tool in the sense of controlled release, as well as the use of alternative animal models such as, Caenorhabditis elegans, Galleria mellonella and zebrafish (Danio rerio). In this work, linear and short peptides from wasps and scorpions will be tested for in vitro antifungal activity and cytotoxicity. The peptide with the best response in these tests will be selected to be associated with a nanostructured lipid system. The formulation will be characterized and tested in vivo, in which C. elegans, G. mellonella and zebrafish will be infected and the efficacy and toxicity will be assessed by observing the survival and fungal load of the animals.

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)

SINGULANI, JUNYA DE LACORTE; OLIVEIRA, LARIANE TEODORO; RAMOS, MARINA DORISSE; FREGONEZI, NATHALIA FERREIRA; GOMES, PAULO CESAR; GALEANE, MARIANA CRISTINA; PALMA, MARIO SERGIO; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. he Antimicrobial Peptide MK58911-NH2 Acts on Planktonic, Biofilm, and Intramacrophage Cells of Cryptococcus neoforman. Antimicrobial Agents and Chemotherapy, v. 65, n. 12, NOV 2021. (16/16212-5, 17/06658-9)

SINGULANI, JUNYA DE LACORTE; GALEANE, MARIANA CRISTINA; RAMOS, MARINA DORISSE; GOMES, PAULO CESAR; DOS SANTOS, CLAUDIA TAVARES; DE SOUZA, BIBIANA MONSON; PALMA, MARIO SERGIO; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. Antifungal Activity, Toxicity, and Membranolytic Action of a Mastoparan Analog Peptide. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, DEC 6 2019. (16/16212-5, 17/06658-9)

OLIVEIRA, LARIANE TEODORO; MEDINA-ALARCON, KAILA PETRONILA; SINGULANI, JUNYA DE LACORTE; FREGONEZI, NATHALIA FERREIRA; PIRES, REGINA HELENA; ARTHUR, RODRIGO ALEX; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. Dynamics of Mono- and Dual-Species Biofilm Formation and Interactions Between Paracoccidioides brasiliensis and Candida albicans. FRONTIERS IN MICROBIOLOGY, v. 11, OCT 14 2020. (17/06658-9, 18/15877-9)

SINGULANI, JUNYA L.; SCORZONI, LILIANA; DE OLIVEIRA, HAROLDO C.; MARCOS, CAROLINE M.; ASSATO, PATRICIA A.; FUSCO-ALMEIDA, ANA MARISA; MENDES-GIANNINI, MARIA JOSE S.. Applications of Invertebrate Animal Models to Dimorphic Fungal Infections. JOURNAL OF FUNGI, v. 4, n. 4, DEC 2018. (15/14023-8, 17/06658-9, 16/17048-4)

GALEANE, MARIANA C.; GOMES, PAULO C.; SINGULANI, JUNYA DE L.; DE SOUZA, BIBIANA M.; PALMA, MARIO S.; MENDES-GIANNINI, MARIA J. S.; ALMEIDA, ANA M. F.. Study of mastoparan analog peptides against Candida albicans and safety in zebrafish embryos (Danio rerio). FUTURE MICROBIOLOGY, v. 14, n. 13, p. 1087-1097, SEP 2019. (17/06658-9, 16/11836-0)

FREGONEZI, NATHALIA FERREIRA; OLIVEIRA, LARIANE TEODORO; SINGULANI, JUNYA DE LACORTE; MARCOS, CAROLINE MARIA; DOS SANTOS, CLAUDIA TAVARES; TAYLOR, MARIA LUCIA; MENDES-GIANNINI, MARIA JOSE SOARES; DE OLIVEIRA, HAROLDO CESAR; FUSCO-ALMEIDA, ANA MARISA. Heat Shock Protein 60, Insights to Its Importance in Histoplasma capsulatum: From Biofilm Formation to Host-Interaction. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, JAN 22 2021. (18/15877-9, 15/14023-8, 16/11836-0, 17/06658-9, 16/17048-4)

SINGULANI, JUNYA L.; SCORZONI, LILIANA; DA SILVA, PATRICIA B.; NAZARE, ANA C.; POLAQUINI, CARLOS R.; BAVELONI, FRANCIELE G.; CHORILLI, MARLUS; REGASINI, LUIS O.; FUSCO-ALMEIDA, ANA M.; MENDES-GIANNINI, MARIA J. S.. ntifungal activity and toxicity of an octyl gallate-loaded nanostructured lipid system on cells and nonmammalian animal. FUTURE MICROBIOLOGY, v. 17, n. 4, p. 281-291, MAR 2022. (14/10446-9, 17/06658-9)