AbstractFungal infections caused by opportunistic yeasts and dermatophytes are increasingglobally, largely due to rising immunocompromised populations and emerging antifungalresistance. Fluconazole remains a widely used antifungal agent; however, its therapeuticefficacy is limited by suboptimal bioavailability and the need for sustained drugexposure. The present study aimed to develop and evaluate fluconazole-loadednanoliposomes using the ethanol injection method to enhance antifungal performance andcontrolled drug delivery.Preformulation studies confirmed a stable λmax at 260 nm in both methanol andphosphate buffer (pH 7.4), with good linearity in the range of 2–20 μg/mL (R2 ≈ 0.999).Solubility profiling indicated moderate lipophilicity, justifying the use of a lipid-baseddelivery system. Eight nanoliposomal formulations (F1–F8) were prepared by varyingdrug-to-lipid ratios. The optimized formulation (F6) exhibited a particle size of 150–200nm with uniform distribution, high entrapment efficiency (91.8 ± 1.0%), and cumulativedrug release of 91% over 12 hours. The release profile demonstrated a biphasic pattern,characterized by an initial burst followed by sustained diffusion-controlled release.Morphological studies (SEM and TEM) confirmed spherical, well-dispersed vesicles,while FTIR analysis verified drug–excipient compatibility without chemical interaction.Zeta potential analysis indicated colloidal stability of the formulation. In vitro antifungalevaluation against Candida albicans and Aspergillus niger demonstrated significantlyenhanced zones of inhibition compared to conventional fluconazole, confirmingimproved therapeutic efficacy.Overall, the developed fluconazole-loaded nanoliposomes, particularly formulation F6,represent a promising nanocarrier system for enhanced antifungal delivery. The ethanol injection method proved to be simple, reproducible, and scalable. This approach mayimprove antifungal therapy by enhancing drug entrapment, controlled release, andantifungal activity. Further in vivo studies are warranted to establish clinical translationpotential.
Amar Singh, Kashif Shakeel, Astha Tiwari (Wed,) studied this question.