Subconjunctival Route to Prolong Corticosteroid Delivery

描述(申请人提供)：这项研究建议结膜下注射可生物降解的纳米和微米颗粒，以维持布地奈德-一种皮质类固醇-几个月的眼后段递送。将超低剂量的布地奈德持续输送到眼后段的概念将极大地促进与脉络膜、视网膜和玻璃体等难以到达的组织相关的疾病的治疗。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，有望用于治疗眼部多种炎症性、增生性和新生血管疾病。这项拟议的研究将使PI能够开始用这种有前途的新眼科治疗药物进行研究。在这项研究中，布地奈德颗粒将使用聚乳酸-乙醇酸(PLGA)制备，这是一种用于外科缝线超过30年的可生物降解聚合物。拟议的布地奈德-PLGA结膜下微粒延长布地奈德给药时间的研究可能会促进其他针对后节的治疗药物的给药。这项研究的目的是验证结膜下注射布地奈德-PLGA颗粒将使布地奈德持续给药长达4个月的假说。本研究的具体目的是：(1)制备和表征布地奈德可生物降解微粒，该微粒可释放布地奈德约4个月。(2)在不引起晶状体混浊或高眼压的情况下，确定组织布地奈德浓度是否随布地奈德-聚乙醇酸(PLGA)结膜下注射剂量的增加而增加。本研究包括布地奈德-PLGA微粒的制备和体内给药研究。建议的布地奈德缓释系统可能有益于几种眼部疾病，包括增生性玻璃体视网膜病变、黄斑囊样水肿、黄斑变性、葡萄膜炎、结节病和硬化炎。在这项研究的基础上，PI将提交一份RO-L建议，评估结膜下布地奈德-PLGA颗粒治疗与炎症和/或血管内皮生长因子升高相关的后节疾病。

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.