ENCAPSULATION OF MILTEFOSINE INTO MICROPARTICLES OF ALGINATE AND EVALUATION OF EFFECTS "IN VITRO" AND "IN VIVO" ON MURINE MODEL OF PULMONARY CRYPTOCOCCOSIS

• Grant number: 15/07993-0
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2016 - August 31, 2018
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Kelly Ishida
• Grantee: Kelly Ishida
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Luciana Biagini Lopes

Abstract

The research for new antifungal agents remains a challenge for the scientific community, and synthetic substances and natural products, are the most frequently studied for the development of antifungal. Miltefosine, an alkylphospholipids analog used in the treatment of visceral leishmaniasis, has shown good antifungal activity against different species of yeast and filamentous fungi. However, miltefosine has high toxicity. The use of the pharmaceutical technology, in particular the incorporation of drugs in micro/nanoparticles for improving the efficacy, pharmacokinetics/bioavailability and decreased toxicity of drugs have been increasingly employed in the development of new strategies for the fungal infections treatment. Within this context, we propose in this project the encapsulation of miltefosine in alginate microparticles in order to primarily reduce toxicity, improve bioavailability, and explore the synergistic effect with others antifungal. For this, miltefosine will be incorporated into alginate microparticles produced by emulsification/ gelling technique and analyzed by biophysical methods to obtain physicochemical characteristics to ensure incorporation colloidal stability and biological activity. Subsequently, the antifungal activity of miltefosine in alginate microparticles will be evaluated "in vitro" using biofilms and planktonic cells of Cryptococcos spp., and "in vivo" in murine model of pulmonary cryptococcosis. (AU)

Scientific publications

(8)

(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)

SPADARI, CRISTINA DE CASTRO; VILA, TAISSA; ROZENTAL, SONIA; ISHIDA, KELLY. Miltefosine Has a Postantifungal Effect and Induces Apoptosis in Cryptococcus Yeasts. Antimicrobial Agents and Chemotherapy, v. 62, n. 8, AUG 2018. (15/07993-0)

ROSSI, DIEGO CONRADO PEREIRA; SPADARI, CRISTINA DE CASTRO; NOSANCHUK, JOSHUA DANIEL; TABORDA, CARLOS PELLESCHI; ISHIDA, KELLY. Miltefosine is fungicidal to Paracoccidioides spp. yeast cells but subinhibitory concentrations induce melanisation. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 49, n. 4, p. 465-471, APR 2017. (15/07993-0)

COSTA-FERNANDEZ, SANDRA; MATOS, JENYFFER K. R.; SCHEUNEMANN, GABY S.; SALATA, GIOVANNA C.; CHORILLI, MARLUS; WATANABE, IL-SEI; DE ARAUJO, GABRIEL L. B.; SANTOS, MARINILCE F.; ISHIDA, KELLY; LOPES, LUCIANA B.. Nanostructured lipid carriers containing chitosan or sodium alginate for co-encapsulation of antioxidants and an antimicrobial agent for potential application in wound healing. International Journal of Biological Macromolecules, v. 183, p. 668-680, JUL 31 2021. (14/50928-2, 19/26048-6, 13/16617-7, 15/07993-0, 17/19374-9, 18/13877-1)

MENDES DA SILVA DE BASTIANI, FERNANDA WALT; SPADARI, CRISTINA DE CASTRO; ROCHA DE MATOS, JENYFFER KELLY; SALATA, GIOVANNA CASSONE; LOPES, LUCIANA BIAGINI; ISHIDA, KELLY. Nanocarriers Provide Sustained Antifungal Activity for Amphotericin B and Miltefosine in the Topical Treatment of Murine Vaginal Candidiasis. FRONTIERS IN MICROBIOLOGY, v. 10, JAN 10 2020. (17/19374-9, 15/07993-0, 18/13877-1)

SPADARI, CRISTINA DE CASTRO; MENDES DA SILVA DE BASTIANI, FERNANDA WALT; LOPES, LUCIANA BIAGINI; ISHIDA, KELLY. Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 14, p. 5187-5199, 2019. (13/16617-7, 18/12149-2, 15/07993-0)

PASSOS, JULIA SAPIENZA; DE MARTINO, LUIZA CAPELLO; CARVALHO DARTORA, VANESSA FRANCO; DE ARAUJO, GABRIEL L. B.; ISHIDA, KELLY; LOPES, LUCIANA B.. Development, skin targeting and antifungal efficacy of topical lipid itraconazole. European Journal of Pharmaceutical Sciences, v. 149, JUN 15 2020. (17/04174-4, 14/50928-2, 17/19374-9, 15/07993-0, 18/13877-1, 13/16617-7)

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)

SPADARI, CRISTINA DE CASTRO; LOPES, LUCIANA B.; ISHIDA, KELLY. Potential Use of Alginate-Based Carriers As Antifungal Delivery System. FRONTIERS IN MICROBIOLOGY, v. 8, JAN 30 2017. (13/16617-7, 15/07993-0)