Hyaluronic Acid Coated Nanoemulsions for CD44 Mediated Targeted Antifungal Therapy : Mechanistic Insights, Formulation Strategies & Considerations

The invasive fungal infections continue to be a significant source of morbidity and mortality, especially in immunocompromised patients. Although some antifungal drugs are focused on a broad spectrum of activity, their poor aqueous solubility, erratic oral bioavailability, food-dependent  absorption, and possible systemic toxicity limits clinical utility.  Nanoemulsion has become a delivery system in which the above limitations may be surmounted through a promising strategy of increasing drug solubilization, and intestinal permeability, and favouring lymphatic circulation. Recent developments point to the possibilities of CD44-specific nanoemulsions in antifungal targeted to the site of action .Hyaluronic acid (HA) is a natural agonist of the CD44 receptors that are overexpressed on inflamed, infected and  activated immune cells, facilitates receptor mediated uptake and enhanced tissue localization. HA-coated nanoemulsions  not only increase mucoadhesion and intestinal retention but also enable localized delivery, therefore minimizing off-target toxicity and enhancing therapeutic efficiency. Parameters of critical formulation-such as oil phase selection, surfactant systems, cosurfactants, droplet size optimization (<200 nm), modulation of zeta potential and excipient safety limits shows exemplary functions on stability, augmentation of permeability, and long term safety. Regulatory considerations such as Inactive ingredients Database (IID) limits and chronic exposure safety tests by FDA are required and well assimilated when designing a formulation. This review comprehensively discusses formulation strategies, CD44-mediated targeting mechanisms, physicochemical optimization, safety profiling, regulatory perspectives, and translational challenges of HA-functionalized nanoemulsions for oral delivery of Antifungal drugs. The article further outlines future directions toward precision  antifungal therapy through receptor-targeted nanocarriers.