Lipid Co-Loaded with PGRN and NATA Demonstrated Significantly Enhanced Antifungal and Anti-Inflammatory Activities in the Treatment of Fungal Keratitis.

PURPOSE: To develop a lipid nanoplatform, designated as "PGRN-NATA-LN", for the co-encapsulation of Natamycin (NATA) and Progranulin (PGRN), and to evaluate its efficacy and safety in the treatment of fungal keratitis (FK). METHODS: The characterization of PGRN-NATA-LN was carried out using a Malvern laser particle size analyzer and transmission electron microscopy (TEM). The drug's encapsulation efficiency, loading capacity, and release profile were evaluated through liquid chromatography, ultraviolet spectrophotometry, and ELISA. The cytotoxicity, ocular surface toxicity, and systemic safety of PGRN-NATA-LN were also examined. In vitro studies were performed to investigate the antifungal properties of PGRN-NATA-LN. Furthermore, cell-based assays were conducted to determine the capability of PGRN-NATA-LN to induce macrophage polarization. RESULTS: The particle size of PGRN-NATA-LN is approximately 140 nm, demonstrating a significant loading capacity for both PGRN and NATA. This facilitates the gradual release of NATA and PGRN, thereby reducing the clearance from the ocular surface. In vitro studies have confirmed the potent antifungal activity and anti-inflammatory of PGRN-NATA-LN. Furthermore, in vivo studies demonstrated that PGRN-NATA-LN exhibited superior therapeutic efficacy in treating FK. DISCUSSION: The PGRN-NATA-LN approach represents a promising strategy to enhance drug bioavailability, demonstrating significant potential in the treatment of FK.