Title : Fabrication of chondroitin sulfate functionalized albumin nanoparticles with taurine and necrostatin for targeted glaucoma treatment
Abstract:
Glaucoma is the leading cause of irreversible blindness worldwide, characterized by progressive vision loss due to the selective damage to retinal ganglion cells (RGCs) and their axons. Oxidative stress is generally believed as one key factor of RGCs death. Recently, necroptosis was identified to play a key role in glaucomatous injury. Therefore, depletion of reactive oxygen species (ROS) and inhibition of necroptosis in RGCs has become one of treatment strategies for glaucoma. However, the therapeutic efficacy of existing drugs is limited due to low retinal permeation and low bioavailability due to a short drug retention time. Herein, we designed a chondroitin sulfate functionalized albumin nanoparticle with taurine and necrostatin (CS-NT@Alb NPs) for glaucoma. Chondroitin sulfate enhances the nanoparticles' ability to target specific areas within the eye, allowing for precise drug delivery. Albumin, a biocompatible protein, serves as a stable and safe carrier for the therapeutic agents. Necrostatin, a necroptosis inhibitor, helps prevent cell death in the optic nerve, thus preserving vision. Taurine, with its antioxidant properties, protects retinal cells from damage and supports overall eye health. By combining necrostatin and taurine into single nanoparticles with a sustained drug release for extended period of time with an enhanced corneal permeation which will subsequently scavenge ROS in RGCs both in vitro and in vivo pathological glaucomatous injury model with reduced doses of frequency and superior biosafety. Further, the nanoparticles will effectively inhibit the necroptosis pathway, increasing the survival of RGCs with improved neuroprotection. This targeted treatment of glaucoma via CS-NT@Alb NPs will open a new avenue for the nanomedicine-based therapy of glaucoma.
