Subconjunctival Route to Prolong Corticosteroid Delivery

延长皮质类固醇递送的结膜下途径

• 批准号: 6572681
• 负责人: UDAY B KOMPELLA
• 金额: $ 14.7万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6572681
• 关键词: biodegradable product; cataract; choroid uvea; conjunctiva; corticosteroids; dosage forms; eye disorder chemotherapy; eye pharmacology; glucocorticoids; inflammation; intraocular pressure; laboratory rabbit; microinjections; polymers; retina; scanning electron microscopy; slow release drug; vascular endothelial growth factors; vitreous body

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.

描述（由申请人提供）：本研究提出结膜下注射可生物降解的纳米颗粒和微米颗粒，以维持布地奈德（一种皮质类固醇）输送到眼后段几个月。向眼后段连续输送超低量布地奈德的概念将显着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，可能用于治疗眼部多种炎症、增殖和新生血管疾病。 拟议的研究将使 PI 能够开始利用这种有前途的眼部治疗新治疗剂开展研究。在这项研究中，布地奈德颗粒将使用聚乳酸-乙醇酸 (PLGA) 来制备，PLGA 是一种可生物降解的聚合物，已在手术缝合线中使用了 30 多年。 拟议的关于结膜下布地奈德-PLGA颗粒用于延长布地奈德递送的研究可能会促进其他靶向后段治疗药物的递送。本研究的目的是检验以下假设：结膜下注射布地奈德-PLGA 颗粒将维持布地奈德输送到眼后段长达 4 个月。本研究的具体目的是：（1）制备并表征能够释放布地奈德约四个月的可生物降解颗粒。 (2) 确定组织布地奈德水平是否随着布地奈德-PLGA（聚乳酸-乙醇酸）颗粒结膜下剂量的增加而增加，而不引起晶状体混浊或高眼压。本研究需要制造布地奈德-PLGA颗粒并在体内药物递送研究。所提出的布地奈德递送系统可能有益于多种眼部疾病，包括增殖性玻璃体视网膜病变、囊样黄斑水肿、根据这项研究，PI 将提交一份 RO-1 提案，以评估结膜下布地奈德-PLGA 颗粒治疗与炎症和/或 VEGF 升高相关的眼后段疾病的效果。