Fortified Long-acting Ocular Gel Laden with Nanoformulated Dexamethasone for Dry Eye Therapy

Dry eye disease (DED) is a rampant and multifactorial ocular disorder. Conventional ocular drug delivery faces significant challenges due to the complex ocular pathophysiology, inadequate bioavailability, rapid elimination, high viscosity, and the need for frequent administration. The present study involves the development of a fortified long-acting ocular gel laden with nano-formulated dexamethasone (DEX) for DED treatment by modifying the current artificial tears formulation, Systane® liquid eye gel drops. This modification was divided into two steps: mixing the commercial gel with ocular demulcents, hyaluronic acid (HA) (HA@in-situ gel), then loading it with a combination of free anti-inflammatory DEX and DEX-loaded chitosan (CS)/Pluronic (PL) nanoparticles (DEX-NPs), DEX-NPs-in-HA@in-situ gel. The 31. 22 factorial experimental designs were employed to optimize formulation for DEX-NPs. Morphology and size of optimum DEX-NPs were obtained using DLS and TEM. DEX-NPs showed a particle size of 250 ± 3 nm. DEX-NPs presented sustained release of DEX for about 5 days. The kinetic release profile of the DEX-NPs-in-HA@in-situ gel showed that the loaded gel follows the Korsmeyer Peppas model with R2 = 0.936. In-vivo evaluation involved the examination of histological micrographs of the cornea structure of the dry eye rat model after application of DEX-NPs-in-HA@in-situ gel. The results confirmed discernible improvement of corneal structure compared to the commercial unmodified eye gel. Graphical Abstract