Development of tissue regenerating hydrogel formulations for the treatment of diabetic retinopathy

Diabetic retinopathy is a chronic diabetes related disease that causes changes in the vascular and nerve structures of the eye. Diabetic retinopathy affects 60% to 75% of diabetic patients and can cause blindness in advanced stages. Current therapy methods, such as laser photocoagulation and intraocular needle therapy, destroys the patients' nerve tissues and causes pain during treatment. Other than these treatments, patients can have surgery but surgery may result in visual loss for patients. Tissue regeneration in the degenerated vascular structure of the eye is needed for the treatment of diabetic retinopathy. In the literature, there are hydrogel systems which are produced to provide tissue regeneration in the treatment of various eye diseases and to be used in controlled drug release. The aim of this study was to produce and characterize taurine loaded chitosan hydrogels for tissue regeneration for the treatment of diabetic retinopathy. The reason for choosing taurine for the treatment of diabetic retinopathy in this study is that taurine increases cell proliferation, provides vascularization and has anti-diabetic effect. Cross-linking test, swelling test and viscosity test were performed on the hydrogels prepared in the study. As a result of the tests, the optimum chitosan concentration was %2 and the optimum glutaraldehyde concentration was %4. For the characterization of chitosan hydrogels and taurine confined hydrogels, cross-linking degree test, swelling test, viscosity test, optical microscope, SEM and FTIR analysis were performed. In vitro release test was performed at 25oC and 37oC, pH 7,4 and pH 8,5 for 15 days for taurine confined hydrogels. Optical microscope, SEM and FTIR analysis showed that taurine was successfully confined to hydrogel. In empty hydrogels prepared using chitosan (%2) and glutaraldehyde (%4) at optimum concentration, taurine was found to reduce cross-linking percentage and viscosity and increase swelling percentage. The percentage of crosslinking of the empty hydrogel was %70,64 ± 3,27 and the percentage of crosslinking of the taurine entrapped hydrogel was %61,33 ± 0,58. The viscosity of the empty hydrogel was measured as 2.883.333 ± 12.583,06 cP, and the viscosity of the taurine confined hydrogel was 1.075.000 ± 65.000 cP. The swelling percentage of the empty hydrogel at 37°C and pH 8.5 was found to be %7,72 ± 0,48 at the end of 90 minutes. The swelling percentage of taurine confined hydrogel at 37°C and pH 8,5 was found to be 7,93 ± 0,04 at the end of 90 minutes. According to the findings of in vitro release test, the cumulative release percentage of taurine from hydrogels decreased when pH was 8,5 and temperature increased. The cumulative release of taurine from the hydrogel was found to be %38,47 ± 0,09 at pH 8,5 and 25°C, and %18,69 ± 0,02 at 37°C. An increase in the cumulative release percentage of taurine was observed with increasing pH at body temperature. The cumulative release of taurine from the hydrogel was found to be %15,92 ± 0,21 at pH 7,4 at 37°C and %18,69 ± 0,02 at pH 8,5 at 37°C. Taurine loaded chitosan hydrogels have been successfully prepared and characterized for the treatment of diabetic retinopathy. The findings are thought to be useful for hydrogel studies in tissue engineering technologies.