Tacrolimus nanocrystal-loaded glycyrrhizic acid hydrogel for the treatment of corneal alkali burn.

Corneal alkali burn (CAB) is a severe ophthalmic emergency that causes extensive damage to the ocular surface and anterior segment. Its primary threat lies in visual impairment resulting from poor recovery, which is largely driven by persistent chronic inflammation. Although corticosteroids are commonly used in clinical practice to control inflammation, their long-term use is limited by risks of corneal melting, glaucoma, and delayed epithelial healing. In this study, a glycyrrhizic acid-based supramolecular hydrogel system (GA gel) loaded with tacrolimus nanocrystals (Tac NCs) was developed to provide an anti-inflammatory effect for chronic inflammation intervention. Formulating tacrolimus into nanocrystals not only improved its solubility in tears but also enhanced its binding to mucin, thereby achieving sustained local exposure. Moreover, the GA gel served as a carrier that prolonged precorneal retention, while also exhibiting anti-inflammatory and antioxidant activities, thereby complementing the Tac NCs. In a rat model of CAB, the Tac NCs-loaded GA gel (Tac@ GA gel) significantly promoted corneal epithelial repair, restored stromal transparency, and inhibited neovascularization. In conclusion, the Tac@GA gel represented a promising drug delivery platform for the comprehensive management of chronic ocular surface inflammation.