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Potential Activity of Micafungin and Amphotericin B Co-Encapsulated in Nanoemulsion against Systemic Candida auris
Gabriel Davi Marena1,2, Gabriela Corrêa Carvalho1,2, Alba Ruiz-Gaitán3,4
1Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil.
Abstract:
The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij® 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.
Insights
Nanoemulsions co-encapsulating amphotericin B and micafungin show enhanced efficacy against multidrug-resistant Candida auris infections. This nanotechnology approach offers a promising therapeutic alternative for controlling lethal yeast outbreaks.
Area of Science:
- Mycology
- Nanotechnology
- Infectious Diseases
Background:
- Candida auris is a multidrug-resistant yeast causing severe, often lethal, systemic infections.
- Hospital outbreaks of C. auris are increasing, with limited monotherapy effectiveness.
- Antifungal resistance necessitates novel therapeutic strategies, including nanotechnology-based solutions.
Purpose of the Study:
- To develop and evaluate a nanoemulsion (NEMA) co-encapsulating amphotericin B (AmB) and micafungin (MICA).
- To assess the efficacy of NEMA against Candida auris infections in vivo.
- To explore the potential of nanoemulsions in potentiating antifungal drug combinations.
Main Methods:
- Nanoemulsions (NEs) were formulated using sunflower oil, cholesterol, Brij 58, soy phosphatidylcholine, and PBS.
- In vivo efficacy was tested in immunosuppressed BALB/c mice infected with Candida auris CDC B11903.
- Biochemical assays were performed to evaluate liver and kidney enzyme concentrations.
Main Results:
- Co-encapsulation of AmB and MICA in NEs significantly potentiated antifungal activity.
- NEMA prevented C. auris infection in the lungs and thymus of treated mice.
- Elevated liver and kidney enzyme levels were observed with AmB and MICA treatment.
Conclusions:
- The combination of AmB and MICA within nanoemulsions is an effective therapeutic strategy against C. auris.
- Nanoemulsions enhance the therapeutic potential of antifungal drug combinations.
- NEMA represents a promising alternative for managing C. auris infections.
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