Chitosan-Gelatin Hydrogel Crosslinked With Oxidized Sucrose for the Ocular Delivery of Timolol Maleate

Ocular hypertension due to increased intraocular pressure is a major risk factor for the development of glaucoma. Rapid clearance and low ocular bioavailability are drawbacks of conventional ocular treatments. This requires frequent and long-term application of antiglaucoma drugs which in turn cause local side effects and are a major cause of therapeutic failure due to loss of persistence in using glaucoma therapy. In this study, a semisynthetic, biocompatible, oxidized sucrose crosslinker was developed and used in the formulation of chitosan-gelatin hydrogel for the sustained release of timolol to control ocular hypertension. The swelling properties of the hydrogel showed a strong relationship with the oxidized sucrose concentration. Mucoadhesive properties of the hydrogel were studied and the in vitro release profiles demonstrated that crosslinking with oxidized sucrose reduced the release rate of the entrapped timolol. The results of both in vitro and in vivo studies supported that the formulated hydrogel maintained the release and in turn the efficacy of timolol for a longer period of time compared to the conventional eye drops. This is expected to reduce the frequency of drug application onto the eye surface and in turn enhances patients' convenience. In conclusion, the developed formulation represents a promising platform for an effective and compliant treatment of ocular hypertension.