Multifunctional Pluronic F-127 Gels Loaded With PEDF, Tacrolimus, and Tobramycin for Advanced Corneal Disease Treatment

Corneal transplantation is a common surgical procedure for restoring vision in patients with severe corneal diseases. However, post-operative complications, including inflammation, immune rejection, and fibrosis, pose significant challenges to the long-term success of corneal transplants. This study aims to develop and evaluate new composite ophthalmic gels combining Tobramycin, Tacrolimus, and pigment epithelium-derived factor (PEDF) for enhancing post-transplant recovery. Four formulations-Tobramycin/PF127, Tobramycin/PEDF/PF127, Tobramycin/Tacrolimus/PF127, and Tobramycin/PEDF/Tacrolimus/PF127 were prepared and evaluated for their effects on human corneal epithelial cells (HCE-T) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assays revealed that PEDF-containing gels significantly promoted HCE-T cell proliferation and migration, while Tacrolimus exhibited strong immunosuppressive properties, reducing immune activation and promoting a stable healing environment. Additionally, PEDF demonstrated potent anti-angiogenic effects, suppressing tube formation in HUVECs. A 60-day rabbit corneal transplantation model further confirmed the therapeutic potential of the composite gels. Gels containing PEDF and Tacrolimus significantly improved corneal transparency, reduced inflammation and fibrosis, and minimized immune rejection. These findings suggest that Tobramycin/PEDF/Tacrolimus/PF127 gel holds promise as an advanced post-operative treatment, offering a comprehensive approach to addressing the challenges of corneal transplant recovery by enhancing cell proliferation, reducing immune responses, and preventing fibrosis and angiogenesis.