Anti-Candida auris activity in vitro and in vivo of micafungin loaded nanoemulsions

Author(s)

Marena, Gabriel Davi ; Carvalho, Gabriela Correa ; Ramos, Matheus Aparecido dos Santos ; Chorilli, Marlus ; Bauab, Tais Maria

• Document type: Journal article
• Source: Medical Mycology; v. 61, n. 2, p. 11-pg., 2023-02-03.

Abstract

Fungi are becoming increasingly resistant, especially the new strains. Therefore, this work developed nanoemulsions (NE) containing micafungin (MICA), in order to improve its action against infections caused by Candida auris. The NEs were composed of the surfactants polyoxyethylene (20) cetyl ether (Brij 58((R)))/soy phosphatidylcholine at 10%, sunflower oil/cholesterol at 10%, and 80% PBS. The NEs were characterized by Dynamic Light Scattering (DLS). For the microbiological in vitro evaluation the determination of the minimum inhibitory concentration (MIC), ergosterol/sorbitol, time kill and biofilms tests were performed. Additionally, the antifungal activity was also evaluated in a Galleria mellonella model. The same model was used in order to evaluate acute toxicity. The NE showed a size of similar to 42.12 nm, a polydispersion index (PDI) of 0.289, and a zeta potential (ZP) of -3.86 mV. NEM had an average size of 41.29 nm, a PDI of 0.259, and a ZP of -4.71 mV. Finally, both nanoemulsions showed good stability in a storage period of 3 months. Although NEM did not show activity in planktonic cells, it exhibited action against biofilm and in the in vivo infection model. In the alternative in vivo model assay, it was possible to observe that both, NEM and free MICA at 0.2 mg/l, was effective against the infection, being that NEM presented a better action. Finally, NEM and free MICA showed no acute toxicity up to 4 mg/l. NEM showed the best activities in in vitro in mature antibiofilm and in alternative in vivo models in G. mellonella. Although, NEs showed to be attractive for MICA transport in the treatment of infections caused by C. auris in vitro and in vivo studies with G. mellonella, further studies should be carried out, in mice, for example. Lay Summary Candida auris is a fungus that can cause infections in the human body. As it is a microorganism with a high potential for resistance, it is extremely important to develop new therapeutic alternatives. Thus, nanotechnology, the science that studies materials with extremely small sizes, can be considered a promising method in the treatment of these infections. (AU)

• FAPESP's process: 19/26821-7 - Nano-in-nano containing curcumin and benzydamine hydrochloride for the treatment of Vulvovaginal Candidiasis: from development to biological application in vitro and in vivo
• Grantee: Gabriela Corrêa Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/09831-9 - Nanoemulsion for co-encapsulation on amphotericin B and micafungin: development and characterizations of the in vitro and in vivo Candida auris potential.
• Grantee: Gabriel Davi Marena
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/23442-2 - Evaluation of the potential of liposomes for co-encapsulation of amphotericin B and micafungin in the treatment of systemic infection caused by Candida auris
• Grantee: Matheus Aparecido dos Santos Ramos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral