This study proposes subconjunctivally injectable biodegradable nano- and micro-particles to sustain the delivery of budesonide, a corticosteroid, to the posterior segment of the eye for a few months. The concept of continuous delivery of ultra-low amounts of budesonide to the posterior segment of the eye will significantly advance the therapy of disorders associated with difficult to reach tissues such as choroid, retina, and vitreous. Budesonide, a very potent corticosteroid with high local activity, low systemic activity, and vascular endothelial growth factor (VEGF)-inhibitory activity, is likely to find application in treating multiple inflammatory, proliferative, and neovascular disorders of the eye. The proposed study will enable the PI to begin establishing his research with this promising new therapeutic agent for ocular therapies. In this study, budesonide particles will be prepared using poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer that has been used in surgical sutures for over 30 years. The proposed research on subconjunctival budesonide-PLGA particles for prolonged budesonide delivery is likely to advance the delivery of other therapeutic agents targeted to the posterior segment. The objective of this study is to test the hypothesis that subconjunctival injection of budesonide-PLGA particles will sustain budesonide delivery to the posterior segment for up to 4 months. The specific aims of this study are: (1) To prepare and characterize biodegradable particles capable of releasing budesonide for about four months. (2) To determine whether the tissue budesonide levels increase with increasing subconjunctival dose of budesonide-PLGA(poly(lactic-co-glycolic acid) particles, without inducing lens opacities or ocular hypertension. This study entails fabrication of budesonide-PLGA particles and in vivo drug delivery studies. The proposed budesonide-delivery system is likely to benefit several disorders of the eye including proliferative vitreoretinopathy, cystoid macular edema, macular degeneration, uveitis, sarcoidosis, and scleritis. Based on this study, the PI will submit an RO-l proposal to assess subconjunctival budesonide-PLGA particles for the therapy of posterior segment disorders associated with inflammation and/or VEGF elevation.
NIH ExPorter
NIH ExPorter