Regenerative Redox Nanodrugs For The Preliminary Study Of Treating Diabetic Cataract

Diabetic cataract is one of the most common complications of diabetes and the leading cause of blindness.The cataract is prone to occur at an early stage and develop rapidly in diabetic patients,which seriously impairs the vision of diabetic patients.At present,the main treatment method is surgery,which is commonly used in the late stage and more serious complications may occur after surgery.However,there are limited drugs for delaying and preventing diabetic cataract in the early stage,such as poor water solubility,low bioavailability,and short retention time severely limit the effective use of drugs in the eyes.In this work,we developed a kind of regenerative redox nanodrugs,which can alleviate cataract in diabetic rats by local treatment of subconjunctival injection.The main contents are as follows:（1）Preparation and characterization of nanodrugs PCNPs.The PEG-PLGA polymers and CeO₂ NPs were successfully self-assembling with an ultrasonic emulsification method to form nanodrugs PCNPs.The PCNPs dispersed as individual particles with the spherical structure,and the particle size was about 100 nm.The effective Zeta potential was nearly neutral.The PCNPs had a mixed valence state(Ce³⁺and Ce⁴⁺),antioxidant property and regenerative redox ability as CeO₂ NPs.（2）Antioxidant and anti-glycation properties of nanodrugs PCNPs in vitro.The results showed that the PCNPs performed less cytotoxicity against human lens epithelial cells,and PCNPs could work not only as antioxidant to protect lens epithelial cells from oxidative stress,but also as glycation inhibitor effectively restrainingα-crystallin glycation and crosslinking.（3）Ocular retention,distribution and safety of nanodrugs PCNPs.The results show that the PNPs can be retained in the eye for a long time by the subconjunctival injection and made nanodrug PCNPs to protect the lens from oxidative damage and glycation for a long time.Meanwhile,we could observe that there was no obvious inflammation or pathological abnormalities even in the conjunctiva and other major organs tissues by SC injection of nanodrugs PCNPs,which can be utilized in subsequent animal treatment experiments.（4）Nanodrugs PCNPs for alleviating cataract in diabetic rats.We successfully established the STZ-induced diabetic rat model.Animal treatment experiments and histopathology results demonstrated that high concentrations of PCNPs significantly alleviated the development of cataract by local SC injection.Moreover,in the lens tissue,the content of malondialdehyde（MDA）was decreased,the level of glutathione（GSH）was increased,the production of protein carbonyl was reduced,and the formation of AGEs pentosidine was inhibited.In short,the regenerative redox nanodrugs PCNPs could work as antioxidant and glycation inhibitor to alleviate cataract in diabetic rats,and provide new ideas for the treatment of ophthalmic diseases such as diabetic cataract.