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. 2024 Jun 28;13(7):549.
doi: 10.3390/pathogens13070549.

Sunflower Oil and Cholesterol Nanoemulsion: A Novel Carrier for Micafungin to Combat Multi-Resistant Candida auris

Gabriel Davi Marena  1   2   3 , Alejandro López  1 , Gabriela Corrêa Carvalho  2   3 , María Del Pilar Marín  4 , María Dolores Pérez Ruiz  5 , Jose Manuel Pérez-Royo  1 , María Ángeles Tormo-Mas  1 , Patricia Bernabé  1 , Eulogio Valentín  1   6 , Taís Maria Bauab  3 , Marlus Chorilli  2 , Javier Pemán  1   7 , Alba Ruiz-Gaitán  1   7
Affiliations

Sunflower Oil and Cholesterol Nanoemulsion: A Novel Carrier for Micafungin to Combat Multi-Resistant Candida auris

Gabriel Davi Marena et al. Pathogens. .

Abstract

Candida auris is an emerging, multidrug-resistant yeast that causes systemic infections, mainly in hospitalized or immunosuppressed patients. This pathogen has a high mortality and morbidity rate. This study aims to evaluate the antifungal potential of micafungin (MICA) encapsulated in a nanoemulsion (NEM) against four clades of C. auris and other non-C. auris species. The antifungal potential of MICA and NEM was evaluated by determining mature biofilm inhibition (0.78-50 µg/mL). The antifungal activities of MICA and NEM (5.92 mg/Kg) were evaluated using an in vivo model of Galleria mellonella. The results showed that NEM intensified the antibiofilm action of MICA, especially in 48 h mature biofilms. In vivo results displayed a higher effectiveness of NEM against all clades of C. auris tested, inhibiting the fungal load in the hemolymph and tissues of G. mellonella with a difference of 3 log10. In addition, C. auris infection caused granulomas surrounded by hemocytes, mainly at the lower and upper ends. Conversely, C. albicans developed pseudohyphae, biofilms, filaments, and chlamydospores. In conclusion, encapsulation of MICA in a nanoemulsion enhances its antifungal activity against mature biofilms of C. auris. This strategy may be considered a therapeutic approach for the control of infections and the dissemination of this new global health threat.

Keywords: Candida auris; Galleria mellonella; emerging infections; micafungin; nanoemulsion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Pre-adherent Candida spp. biofilms treated with MICA and NEM. MICA: micafungin; NEM: nanoemulsion + micafungin; NE: nanoemulsion; GC: growth control. (****): Statistical difference between the treated group (MICA and NEM) and the untreated group (GC and NE). Asterisk in red indicates difference between treated groups. Black asterisk indicates difference with the infection control group. (*) p = 0.05; (**) p = 0.005; (***) p = 0.0005; and (****) p < 0.0001.
Figure 2
Figure 2
Mature biofilm of Candida spp. treated with MICA and NEM. MICA: micafungin; NEM: nanoemulsion + micafungin; NE: nanoemulsion; GC: growth control. (****): Statistical difference comparing the treated group (MICA and NEM) with the untreated group (GC and NE). Asterisk in red indicates difference between treated groups. Black asterisk indicates difference with the infection control group; (*) p = 0.05; (**) p = 0.005; (***) p = 0.0005 and (****) p < 0.0001.
Figure 3
Figure 3
Metabolic activity by confocal microscopy analysis of C. auris biofilms treated with MICA and NEM. (A,B) Control; (C,D) biofilms treated with micafungin; (E,F) biofilms treated with nanoemulsion + micafungin.
Figure 4
Figure 4
Antifungal activity of MICA and NEM against C. auris and non-C. auris in G. mellonella hemolymph and tissues. (A–F): Hemolymph; (G–L): tissue; NE: nanoemulsion; PBS+AmP: basic phosphate solution + ampicillin (20 µg/mL); MICA: micafungin; NEM: nanoemulsion + micafungin; absence of letters: no statistical difference; letter (a): the difference between infection groups (NE and PBS+AmP) with treated groups (MICA and NEM); letter (b): difference with the infection group and difference with MICA.
Figure 4
Figure 4
Antifungal activity of MICA and NEM against C. auris and non-C. auris in G. mellonella hemolymph and tissues. (A–F): Hemolymph; (G–L): tissue; NE: nanoemulsion; PBS+AmP: basic phosphate solution + ampicillin (20 µg/mL); MICA: micafungin; NEM: nanoemulsion + micafungin; absence of letters: no statistical difference; letter (a): the difference between infection groups (NE and PBS+AmP) with treated groups (MICA and NEM); letter (b): difference with the infection group and difference with MICA.
Figure 5
Figure 5
Histopathological findings in G. mellonella tissues infected with C. auris and non-C. auris and stained with PAS and HE (×100). Hematoxylin–eosin: (A) InP13; (B) JAP 1; (C) SP96; (D) VEN C6; (E) C. albicans; (F) C. parapsilosis. Periodic acid–Schiff: (G) InP13; (H) JAP 1; (I) SP96; (J) VEN C6; (K) C. albicans; (L) phosphate buffer + C. parapsilosis.
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