Abstract
Ganciclovir (GCR), an antiviral drug used to treat herpetic keratitis, is less effective because of its poor bioavailability (BCS III). Nanosuspension (NS) is a promising technique for improving solubility and the dissolution of poorly soluble drugs by size reduction. Topical solution or conventional eye drop represents the easiest route to deliver drugs to the anterior eye segment; however, low precorneal retention, high nasolacrimal drainage, and metabolic degradation lead to low bioavailability. To overcome these limitations, incorporating GCR-NS into mucoadhesive in situ gel-forming (ISG) could enhance its ocular permeability and drug bioavailability. Therefore, this study aimed to design and optimize GCR-NS-loaded in situ gelling mucoadhesive eye drops (GCR-NS-loaded mucoadhesive ISG) for improving ophthalmic delivery. Pluronic® F127 (P127), an ophthalmic gel forming, was selected as a polymer due to self-gelling formation by temperature-triggered in situ gelling at ocular temperature. Moreover, hyaluronic acid-modified catechol (HA-cat), a novel mucoadhesive polymer, was combined to achieve the desired ocular mucoadhesion and facilitate ophthalmic delivery. Optimized GCR-NS formulation prepared using the nanoprecipitation technique was selected based on the central composite design (CCD) model by evaluating their particle size, polydispersity index (PDI), and zeta potential, before being loaded into mucoadhesive ISG. The optimal GCR-NS-loaded mucoadhesive ISG (F7) revealed the desired physicochemical properties with better viscosity, mucoadhesion, and gelling capacity at physiological conditions, high ocular permeation with a sustained manner over 24 h compared to eye drop suspension. Accordingly, GCR-NS-loaded mucoadhesive ISG could be a promising ocular delivery system for the effective local delivery of GCR for herpetic keratitis. Keywords: Ganciclovir, Nanosuspension, Mucoadhesive eye drop, Ophthalmic delivery, In situ gelling
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