Evaluation of the potential of liposomes for co-encapsulation of amphotericin B and micafungin in the treatment of systemic infection caused by Candida auris

• Grant number: 18/23442-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2019
• Effective date (End): July 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Matheus Aparecido dos Santos Ramos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM

Abstract

The Candida auris species has been prominent in the medical field in recent years due to its involvement in cases of systemic infections, mainly in the nosocomial environment. Authorities around the world remain alert to the rapid progression of pathological conditions attributed to this species due to the scarcity of available drug approaches for treatment. Thus, new research for therapeutic alternatives has been explored in recent years, mainly in the area of Pharmaceutical Nanotechnology. Liposomes are classified as an important drug delivery system aiming primarily at optimizing the pharmacological properties of bioactive principles as well as reducing levels of toxicity. The versatility of this system attracts research in several areas of science, especially microbiology, since antimicrobial drugs with therapeutic restrictions are optimized for use in therapies of severe infections. The aim of this work is to evaluate the potential of liposomes for the co-encapsulation of amphotericin B (AMB) and micafungin (MICA), two important drugs widely used in candidemia therapy, aiming at the treatment of systemic infections triggered by C. auris. The liposomes will be synthesized from cholesterol, soybean phosphatidylcholine and PBS buffer by hydration techniques of the lipid film for the encapsulation of MICA and AMB. Physical-chemical characterization tests (transmission electron microscopy, determination of mean particle diameter, zeta potential, polydispersity index, in vitro release assays and encapsulation efficiency) will be performed. Biological analyzes to evaluate inhibitory potential in vitro against C. auris (determination of activity against planktonic cells, fungicidal inhibition kinetics, inhibition of mature and forming biofilms, ergosterol-sorbitol interaction assays, combination assays and resistance development) will be performed with MICA and AMB free and co-encapsulated in liposomes, as well as toxicity experiments (in vitro cytotoxicity on cell lines and in vivo alternative model of acute toxicity in Gallerea melonella) and experimental in vivo assay (in vivo experimental trial of C. auris candidemia therapy) will be developed. In summary, this work will seek to reach new perspectives in the treatment of systemic infections caused by C. auris, presenting a new therapeutic approach for available drugs.

Scientific publications

(12)

(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)

DOS SANTOS RAMOS, MATHEUS APARECIDO; DOS SANTOS, KAREN CRISTINA; DA SILVA, PATRICIA BENTO; DE TOLEDO, LUCIANI GASPAR; MARENA, GABRIEL DAVI; RODERO, CAMILA FERNANDA; FURQUIM DE CAMARGO, BRUNA ALMEIDA; FORTUNATO, GIOVANNA CAPALDI; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Nanotechnological strategies for systemic microbial infections treatment: A review. International Journal of Pharmaceutics, v. 589, NOV 15 2020. (14/50928-2, 18/23442-2)

DOS SANTOS RAMOS, MATHEUS APARECIDO; DE TOLEDO, LUCIANI GASPAR; SPOSITO, LARISSA; MARENA, GABRIEL DAVI; DE LIMA, LAURA CAMINITTI; FORTUNATO, GIOVANNA CAPALDI; ARAUJO, VICTOR HUGO SOUSA; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Nanotechnology-based lipid systems applied to resistant bacterial control: A review of their use in the past two decades. International Journal of Pharmaceutics, v. 603, JUN 15 2021. (18/23442-2, 14/50928-2)

MARENA, GABRIEL DAVI; DOS SANTOS RAMOS, MATHEUS APARECIDO; LIMA, LAURA CAMINITTI; CHORILLI, MARLUS; BAUAB, TAIS MARIA. alleria mellonella for systemic assessment of anti-Candida auris using amphotericin B loaded in nanoemulsio. Science of The Total Environment, v. 807, n. 3, FEB 10 2022. (18/23442-2, 14/50928-2, 19/09831-9)

MARENA, GABRIEL DAVI; DOS SANTOS RAMOS, MATHEUS APARECIDO; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Biological Properties and Analytical Methods for Micafungin: A Critical Review. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, v. 51, n. 4, FEB 2020. (18/23442-2)

DE LIMA, LAURA C.; RAMOS, MATHEUS A. S.; DE TOLEDO, LUCIANI G.; RODERO, CAMILA F.; HILARIO, FELIPE; DOS SANTOS, LOURDES C.; CHORILLI, MARLUS; BAUAB, TAIS M.. Syngonanthus nitens (Bong.) Ruhland Derivatives Loaded into a Lipid Nanoemulsion for Enhanced Antifungal Activity Against Candida parapsilosis. CURRENT PHARMACEUTICAL DESIGN, v. 26, n. 14, p. 1556-1565, 2020. (18/23442-2, 17/18435-4)

MARENA, GABRIEL DAVI; DOS SANTOS RAMOS, MATHEUS APARECIDO; CARVALHO, GABRIELA CORREA; DE LIMA, LAURA CAMINITTI; CARNEIRO SOARES DO NASCIMENTO, ANDRE LUIZ; SABIO, RAFAEL MIGUEL; RODERO, CAMILA FERNANDA; SPOSITO, LARISSA; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Development and characterization of an amphotericin B - loaded nanoemulsion applied to Candida auris biofilms control. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 74, p. 14-pg., 2022-07-20. (19/26821-7, 18/25377-3, 19/09597-6, 19/09831-9, 18/23442-2, 14/50928-2, 17/22758-3, 18/23357-5)

MARENA, GABRIEL DAVI; RAMOS, MATHEUS APARECIDO DOS SANTOS; BAUAB, TAIS MARIA; CHORILLI, MARLUS. A Critical Review of Analytical Methods for Quantification of Amphotericin B in Biological Samples and Pharmaceutical Formulations. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, SEP 2020. (14/50928-2, 18/23442-2)

MARENA, GABRIEL DAVI; FONSECA-SANTOS, BRUNO; MATHEUS APARECIDO DOS SANTOS, RAMOS; DOS SANTOS, KAREN CRISTINA; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Incorporation of Ursolic Acid in Liquid Crystalline Systems Improves the Antifungal Activity AgainstCandidaSp. JOURNAL OF PHARMACEUTICAL INNOVATION, JUL 2020. (18/23442-2)

MARENA, GABRIEL DAVI; CARVALHO, GABRIELA CORREA; RAMOS, MATHEUS APARECIDO DOS SANTOS; CHORILLI, MARLUS; BAUAB, TAIS MARIA. Anti-Candida auris activity in vitro and in vivo of micafungin loaded nanoemulsions. Medical Mycology, v. 61, n. 2, p. 11-pg., 2023-02-03. (19/26821-7, 19/09831-9, 14/50928-2, 18/23442-2)

MARENA, GABRIEL DAVI; RAMOS, MATHEUS APARECIDO DOS SANTOS; CARVALHO, GABRIELA CORREA; PARIS JUNIOR, JOSE ALBERTO; RESENDE, FLAVIA APARECIDA; CORREA, IONE; ONO, GABRIELA YUKI BRESSANIM; SOUSA ARAUJO, VICTOR HUGO; DE CAMARGO, BRUNA ALMEIDA FURQUIM; BAUAB, TAIS MARIA; et al. Natural product-based nanomedicine applied to fungal infection treatment: A review of the last 4 years. Phytotherapy Research, v. 36, n. 7, p. 36-pg., 2022-05-29. (18/23442-2, 14/50928-2, 19/09831-9)

MARENA, GABRIEL DAVI; RAMOS, MATHEUS APARECIDO DOS SANTOS; BAUAB, TAIS MARIA; CHORILLI, MARLUS. A Critical Review of Analytical Methods for Quantification of Amphotericin B in Biological Samples and Pharmaceutical Formulations. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, v. 52, n. 3, p. 22-pg., 2020-09-01. (14/50928-2, 18/23442-2)

MARENA, GABRIEL DAVI; FONSECA-SANTOS, BRUNO; MATHEUS APARECIDO DOS SANTOS, RAMOS; DOS SANTOS, KAREN CRISTINA; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Incorporation of Ursolic Acid in Liquid Crystalline Systems Improves the Antifungal Activity AgainstCandidaSp. JOURNAL OF PHARMACEUTICAL INNOVATION, v. 16, n. 4, p. 11-pg., 2020-07-10. (18/23442-2)