Development and Evaluation of a Diclofenac-Loaded Thermogel for Topical Treatment of Corneal Alkali Burns

Abstract

Corneal alkali burns have become a frequent and urgent issue in ophthalmology, but current treatments are limited. To address this, a diclofenac-loaded thermogel with anti-inflammatory agents is developed to target inflammation and improve drug delivery for corneal alkali burns. Thermogels are prepared by dissolving methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) in phosphate-buffered saline (PBS), adding diclofenac (DF), and storing the solution at 4 °C. The thermogel's temperature-sensitive behavior and injectability at 35 °C are assessed. Freeze-dried thermogels are examined using scanning electron microscopy. Rheological properties, swelling behavior, and in vitro release studies are conducted. In vitro and in vivo biocompatibility tests are performed. A corneal alkali burn model is established in rats, and different treatments are administered for 7 days. Eyeballs are collected for histological and molecular analysis. The thermogel formulation formed a stable gel at 35 °C and continuously released DF for 7 days. In vitro and in vivo tests confirmed the thermogels' excellent biocompatibility. The released DF promotes the expression of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibits the expression of pro-inflammatory factors TNF-α and vascular endothelial growth factor (VEGF). This novel DF/thermogel offers an efficient, topical, and cost-effective approach with significant potential for treating corneal alkali burns.