Subconjunctival Route to Prolong Corticosteroid Delivery

描述（由申请人提供）：本研究建议使用结膜下可注射的可生物降解纳米和微颗粒来维持布地奈德（一种皮质类固醇）在眼后段的递送数月。将超低剂量布地奈德持续输送到眼后段的概念将显著推进与难以到达的组织（如脉络膜、视网膜和玻璃体）相关的疾病的治疗。布地奈德是一种非常有效的皮质类固醇，具有高局部活性，低全身活性和血管内皮生长因子（VEGF）抑制活性，可能用于治疗眼部的多种炎症、增殖和新生血管疾病。拟议的研究将使PI开始建立他的研究与这种有前途的新治疗剂的眼部治疗。在本研究中，布地奈德颗粒将使用聚乳酸-羟基乙酸（PLGA）制备，PLGA是一种可生物降解的聚合物，已用于手术缝合线超过30年。提出的布地奈德- plga结膜下颗粒延长布地奈德给药的研究可能会促进其他靶向后段治疗药物的递送。本研究的目的是验证结膜下注射布地奈德- plga颗粒将维持布地奈德后段递送长达4个月的假设。本研究的具体目的是：(1)制备并表征布地奈德缓释约4个月的可生物降解颗粒。(2)观察组织布地奈德水平是否随着布地奈德-聚乳酸-羟基乙酸颗粒结膜下剂量的增加而升高，而不引起晶状体混浊或高眼压。这项研究需要布地奈德- plga颗粒的制造和体内给药研究。拟议的布地奈德给药系统可能有益于几种眼睛疾病，包括增殖性玻璃体视网膜病变、囊样黄斑水肿、黄斑变性、葡萄膜炎、结节病和巩膜炎。基于这项研究，PI将提交一份RO-l提案，评估布地奈德- plga结膜下颗粒治疗与炎症和/或VEGF升高相关的后段疾病。

DESCRIPTION (provided by applicant): 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.