Abstract

The emerging pathogen Candida auris is an emerging fungal pathogen that was associated with nosocomial infectious outbreaks. Its worldwide incidence and the emerging multidrug-resistant strains highlight the urgency for novel and effective antifungal treatment strategies. Lippia sidoides essential oil (LSEO) proved antifungal activity, including anti-Candida. However, it may undergo irreversible changes when in contact with external agents without adequate protection. Herein, we encapsulated LSEO in nanostructured lipid carriers (NLC) through the hot emulsification method followed by sonication. NLC matrix was based on oleic acid and Compritol® 888, or a combination of carnauba wax and beeswax, stabilized by sodium dodecyl sulfate. Eight formulations were produced and characterized by the determination of the particle size (213.1 to 445.5 nm), polydispersity index (around 0.3), and ζ-potential (−93.1 to −63.8 mV). The antifungal activity of nanoparticles and LSEO against C. auris and the in vivo toxicity in Galleria mellonella model were also evaluated. Both NLC and LSEO exhibited potent activity against the yeast, with Minimum Inhibitory Concentration between 281 and 563 µg/mL, and did not evidence toxicity in the in vivo model. Therefore, this study confirms the viability of NLCs loaded with LSEO in combating drug-resistant pathogens as a potential new therapeutic strategy for managing of candidemia.

Highlights

  • Published: 13 January 2022Since 2009, when it was first isolated in Japan [1], Candida auris became a major concern to medical mycology, emerging across the globe in more than 40 countries, being transmissible, and associated with high mortality rates [2,3,4]

  • We propose to use the nanostructured lipid carriers (NLC) as a delivery system to encapsulate L. sidoides EO and evaluate its potential as an antimicrobial agent in combating the C. auris’ multidrug resistant pathogen

  • The gas chromatography coupled to mass spectroscopy (GC-MS) analysis allowed the identification of twenty-six components in the Lippia sidoides essential oil (LSEO)

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Summary

Introduction

Since 2009, when it was first isolated in Japan [1], Candida auris became a major concern to medical mycology, emerging across the globe in more than 40 countries, being transmissible, and associated with high mortality rates [2,3,4]. C. auris diagnostics in resource-limited countries is another challenge, as it involves complex and expensive equipment, such as MALDI-TOF MS [4]. Of particular concern is that the COVID-19 pandemic overwhelmed the healthcare facilities and provides the ideal conditions for new outbreaks of C. auris infection, causing an increase in the patients’ mortality rates [8,9]. C. auris presents an even more challenging treatment profile, as it can develop different resistance mechanisms, such as drug target mutation and overexpression, activation of stress response pathways, biofilm

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