Unlocking Multidrug Resistance in Fungal Keratitis Using Lipid-BasedDrug Delivery System

Fungal keratitis is the leading cause of corneal blindness, particularly in the tropics and subtropical regions where fungal infections such as Aspergillus, Candida, and Fusarium are highly prevalent. Ocular trauma, wearing contact lenses, chronically infected surface issues, or excessive exposure to corticosteroids are all frequent causes of fungal keratitis. The clinical symptoms include edematous ulcers, photophobia, stromal infiltrates, and impaired vision. The emergence of multidrug resistance to first-line antifungals such as natamycin, voriconazole, and amphotericin B significantly complicates the clinical management. The mechanisms of resistance are activation of efflux pumps, biofilm formation, formation of corneal tissues, and subtherapeutic penetration of drugs because of tear removal that takes place rapidly. Conventional medicines are often prone to epithelial toxicity, poor tissue penetration, and low solubility, leading to low adherence and therapeutic effectiveness. Lipid-based drug delivery systems, including solid lipid nanoparticles, nanostructured lipid carriers, and liposomes, could overcome such problems. Lipid-based delivery systems may enhance corneal residence time, improve bioavailability, reduce dosing frequency, and prevent systemic exposure. Further, in preclinical research, it is established that anti-fungal drugs, when packaged with lipid carriers, exhibit improved therapeutic efficacy and tissue distribution. Several lipid-based formulations have also destroyed fungal biofilms and may therefore help address aspects of multidrug resistance. However, much of the evidence remains preclinical, and translation into clinical practice is hindered by instability, regulatory constraints, and manufacturing costs. This review objectively examines lipid systems, describes MDR processes, and emphasizes translation constraints.