Formulation and Evaluation of Niosomal Gel Containing Itraconazole And Tea Tree Oil for Enhanced Topical Antifungal Therapy

Fungal infections of the skin and mucous membranes remain a persistent clinical challenge due to their chronicity, recurrence, and increasing resistance to conventional antifungal drugs. Itraconazole, a triazole antifungal agent, demonstrates broad-spectrum efficacy against dermatophytes, Candida species, and Aspergillus infections. However, its limited aqueous solubility and poor skin permeability have restricted its topical application. In recent years, vesicular drug delivery systems such as niosomes have emerged as promising carriers for improving dermal and transdermal drug delivery. These surfactant-based vesicles enhance drug deposition in the skin, prolong retention, and minimize systemic absorption. The incorporation of tea tree oil (Melaleuca alternifolia), a natural essential oil with strong antifungal and anti-inflammatory properties, offers a synergistic approach when combined with itraconazole. The development of a niosomal gel containing both agents can overcome the limitations of conventional topical formulations by improving drug solubility, permeability, and stability while maintaining localized action. This review discusses the formulation strategies, physicochemical characterization, in vitro and ex vivo evaluation, antifungal activity, and potential mechanisms underlying the enhanced efficacy of itraconazole and tea tree oil-loaded niosomal gel. Comparative studies with conventional gels and emerging hybrid vesicular systems are also presented. Finally, the review highlights challenges in scaling up, regulatory perspectives, and future prospects for clinical translation of niosomal gels in antifungal therapy.