Development and Evaluation of an Essential Oil-Based Nanoemulgel for Topical Antifungal Activity Against Candida Species

Abstract

Objective: This study aimed to develop and optimize a polymer-based nanoemulgel containing Melaleuca alternifolia (tea tree) and Curcuma longa (turmeric) essential oils and to evaluate its physicochemical properties, in-vitro release characteristics, antifungal activity against Candida albicans and Candida parapsilosis, irritation potential, and short-term stability.

Materials and Methods: A 7:3 ratio of M. alternifolia to C. longa oils was selected as the oil phase. Span 20 and Tween 80 were used at an optimized surfactant mixture (Smix) ratio of 8:2. Nanoemulsion were prepared using ultrasonication and evaluated for physical stability, droplet size, polydispersity index (PDI), zeta potential, conductivity, and morphology. The optimized nanoemulsion was incorporated into a Carbopol 934 gel base to obtain the polymeric nanoemulgel (NEG3). The formulation was characterized for physicochemical properties, essential oil content, in-vitro release, antifungal activity, and irritation potential using the Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Stability was evaluated under real-time and accelerated storage conditions for three months.

Results: The optimized nanoemulsion exhibited a mean droplet size of 155.5 nm, a PDI of 0.184, and a zeta potential of −7.36 mV. Transmission electron microscopy confirmed nanoscale droplets with predominantly elongated-to-elliptical morphology. The optimized nanoemulgel was pale yellow, smooth, homogeneous, and translucent, with a pH of 6.40 ± 0.03, viscosity of 8425 ± 35 cP, spreadability of 14.26 ± 0.41 g·cm/s, and extrudability of 8.15 ± 0.18 g/0.5 min. The measured essential oil contents were 98.84 ± 0.72% for M. alternifolia oil and 97.63 ± 0.65% for C. longa oil. At 24 h, cumulative release reached 76.99 ± 2.50% and 72.57 ± 2.90%, respectively. The Korsmeyer-Peppas model provided the best fit to the release data, with release exponents of 0.62 and 0.58, indicating non-Fickian transport. The formulation exhibited concentration-dependent antifungal activity, producing inhibition zones of 25.00 ± 1.00 mm against C. albicans and 20.00 ± 1.00 mm against C. parapsilosis at 1000 µg/mL. The minimum inhibitory concentration (MIC) was reported as 15.63 µg/mL for both strains. The HET-CAM assay yielded an irritation score of 0.00. The formulation maintained its overall physical characteristics and essential oil content during three months of real-time and accelerated storage.

Conclusion: The developed essential oil-loaded polymeric nanoemulgel demonstrated favorable physicochemical characteristics, sustained in-vitro release, and antifungal activity against both tested Candida species. The absence of detectable irritation in the HET-CAM assay and the maintenance of key formulation characteristics during short-term stability testing support its further investigation as a potential topical antifungal delivery system. Ex-vivo permeation, comprehensive dermal safety, in-vivo efficacy, and long-term stability studies are required before therapeutic application can be established.