Nanoemulsions as emerging antifungal carriers: Potential beyond conventional boundaries

Fungal infections, particularly those caused by Candida species, continue to pose a major clinical challenge, especially in immunocompromised populations.Despite the availability of antifungal agents, their effectiveness is often limited by poor solubility, systemic toxicity, low bioavailability, and increasing resistance particularly to azoles and polyenes.In this context, nanoemulsion-based drug delivery systems have garnered increasing attention as a promising approach to overcome these pharmacokinetic and pharmacodynamic limitations [1,2].Nanoemulsions are kinetically stable colloidal dispersions composed of oil, water, surfactants, and co-surfactants.These systems enhance the solubility and stability of hydrophobic drugs and facilitate their targeted delivery.Their nanoscale droplet size allows for improved penetration through biological barriers, offering both sustained release and reduced systemic exposure [3].Furthermore, surface modification capabilities permit ligand-specific targeting and enhanced interaction with fungal biofilms.The scalability and relatively low production cost of nanoemulsions make them particularly attractive for translational research and application in resource-limited settings [4].Mechanistically, nanoemulsions exert antifungal effects by compromising fungal cell membrane integrity.Surfactants within the formulation destabilize lipid bilayers, leading to membrane leakage and cell death.Their ability to penetrate the extracellular matrix of fungal biofilms increases local drug concentration and efficacy features particularly relevant for biofilm-associated and resistant infections [5][6][7].Recent studies, including one exploring an eucalyptol-based nanoemulsion incorporating amphotericin B, have demonstrated promising anti-biofilm activity against Candida albicans, both in vitro and in infection models such as Galleria mellonella [8].Such findings support the potential of nanoemulsions as an alternative platform to conventional antifungal therapies.