Gauri Misra, Surgery, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, Ravi S. J. Singh, Ophthalmology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, Thomas W. Gardner, Ophthalmology and Cellular & Molecular Physiology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, and Tao L. Lowe, Surgery, Bioengineering, and Materials Science and Engineering, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033.
Diabetic retinopathy involves retinal neuronal cell loss which precedes clinically evident vascular changes. Intensive metabolic control with systemic insulin therapy reduces the risk of development and progression of diabetic retinopathy, but it has potential adverse effects like hypoglycemia. In this project, a novel subconjunctivally implantable hydrogel has been developed for long-term local insulin release to retard the development and progression of early diabetic retinopathy.
These novel hydrogels are composed of N-isopropyl acrylamide and dextran-lactate-2-hydroxyethyl methacrylate with a variety of feeding weight ratios, and are thermo-responsive and hydrolytically degradable. The hydrogels were synthesized by UV photopolymerization and insulin was encapsulated into the hydrogels during the polymerization process. The hydrogels released FITC-insulin in vitro for more than a week and were nontoxic to neuron-like PC-12 cells. Insulin released from the hydrogels retained biologically activity. The hydrogels were well tolerated by male Sprague-Dawley rats after subconjunctival implantation.