Sequential delivery of anti-inflammatory and anti-scar drugs by Rg3 liposome-embedded thiolated chitosan hydrogel eye drops for corneal alkali burn

Corneal injury is a major cause of inflammation, scarring, and even vision loss. The main treatment for corneal injury is local administration of eye drops. However, due to the limitation of the protective barrier of the eyes, conventional eye drops have the disadvantages of low bioavailability, high side effects, and limited efficacy. In this study, the anti-inflammatory agent dipotassium glycyrrhizate (DG) and the antifibrotic agent ginsenoside Rg3 were incorporated into a thermosensitive hydrogel in order to develop a multifunctional hybrid hydrogel eye drops (RDTG) for the synergistic treatment of corneal alkali burn. The hydrogel network was formed by thiolated chitosan and β-glycerophosphate through both physical and chemical crosslinking. DG was distributed in free state in the hydrogel, while Rg3 was incorporated into the hydrogel in the form of liposomes. Furthermore, RDTG showed the characteristic of sequential drug-release. In vivo studies using a mouse model of corneal alkali burn have confirmed that RDTG could effectively reduce inflammation, promote corneal wound healing, and inhibit corneal scar. Therefore, the efficient delivery of RDTG eye drops provided a promising approach for the treatment of corneal alkali burn.