3D Molded Inserts Fabricated Using a Self-Nanoemulsifying Drug Delivery System (SNEDDS) to Increase Voriconazole and Diclofenac Permeation for the Treatment of Corneal Keratitis

Acanthamoeba keratitis (AK) and mycotic keratitis (MK) are severe infectious diseases of the cornea. A major challenge to treatment is the poor bioavailability of conventional eye drop formulations, resulting in significant loss of the therapeutic compound. The present study describes the preparation of self-nanoemulsifying drug delivery systems (SNEDDSs) utilizing 3D-molded inserts as a vehicle for the co-delivery of voriconazole (VOR) and diclofenac sodium (DIC). Characterization of the SNEDDS and the 3D-molded inserts involved analysis of droplet size, polydispersity index (PDI), and zeta potential (ZP), followed by an ex vivo transcorneal permeation. Careful optimization of the SNEDDS composition was fundamental for obtaining a nanoemulsion with a droplet size under 100 nm, a PDI below 0.35, and a variable ZP (ranging from −14.6 ± 0.1 to 16.3 ± 2.4 mV). These properties facilitated a marked improvement in voriconazole’s solubility and subsequent transcorneal permeability. The investigation of the inserts revealed that the in vitro drug release could be tailored for immediate release or extended release. Moreover, ex vivo permeation studies demonstrated that the inserts delivered voriconazole to the cornea at concentrations more than the minimum inhibitory concentration. This work successfully demonstrates the formulation of a patient-centric, personalized drug delivery platform for the treatment of AK and MK.