Evaluation of liposomal hydrocolloidal NPs loaded by tea tree oil as antifungal agent in vitro and in vivo investigations: Preclinical studies

Fungi have a great ability and a wide variety of mechanisms to endure the toxicity of current antifungal agents. Researchers are working to find new therapeutic agents to combat the resistance ability of fungi. Almost all commercial antifungal agents have a wide variety of side effects on human health. This study aims to introduce tea tree oil nanoparticles as antifungal delivery termed TNSAD, which contains hybrid tea tree oil attached chitosan in a liposomal formulation, and assess its antifungal activity using in vitro and in vivo infection models. Tea tree oil was first coated by chitosan, then inserted inside liposomal bilayers, and finally functionalized by a layer of chitosan, forming the TNSAD. The antifungal activity was evaluated against four different invasive, opportunistic, and zoonotic fungal pathogens (Aspergillus flavus, Aspergillus fumigatus, Microsporum gypsum, and Fusarium oxysporum). The cytotoxicity of TNSAD was then tested against the HEp-2 cell line. Finally, the antifungal activity against Aspergillus fumigatus and Microsporum gypsum was assessed in vivo in a rat model. The in vitro results confirm the potency of TNSAD against fungi and its safety at a concentration of ≤ 5 mg/ml. In vivo results revealed that fungal cells were destroyed within the tissue when used systematically. we have described here a natural remarkable design that represents a potential antifungal agent and provided evidence for its efficiency and safety, which makes it a promising antifungal agent for the treatment of systemic and topical fungal infections.