Thermosensitive in situ gel containing alpha-lipoic acid and rutin for the treatment of corneal neovascularization: formulation, characterization, and in vivo evaluation
Özet
Corneal neovascularization (CnV) is a significant ophthalmological condition often leading to discomfort and vision impairment. Due to the limitations and side effects associated with conventional drug therapies for CnV, innovative treatment strategies are being explored. In this study, the potential of alpha-lipoic acid and rutinloaded thermosensitive in situ gels for the treatment of CnV was evaluated. The ocular in situ gel was formulated using the cold method and included chitosan, poloxamer 407, and poloxamer 188 as polymers. A design of experiments (DoE) approach was employed to investigate the effects of formulation variables on critical quality attributes, including pH, gelation temperature, and viscosity. The optimized drug-loaded gel exhibited a pH of 5.05 +/- 0.1, pseudo-plastic flow behavior with a viscosity of 341 +/- 26 cP at 25 degrees C, and gelation at 34 +/- 0.4 degrees C. Drug release followed Weibull and first-order kinetics. Ocular safety was confirmed through in vitro cytotoxicity studies using L929 and ARPE-19 cell lines. In vivo studies in rats and histochemical analyses of the cornea demonstrated that the optimized formulation (Formulation K) was as effective as dexamethasone, a standard treatment for CnV, and further promoted epithelial cell regeneration. Histological evaluations of ocular tissues revealed reduced inflammation and neovascularization in the Formulation K group, supporting its therapeutic potential. Overall, our findings suggest that the developed in situ gel system offers sustained drug release and enhanced therapeutic efficacy for the treatment of corneal neovascularization.
