Ophthalmic drug delivery using a multi-layer contact lens design that enables targeting, constant-rate release and failure protection

项目总结 家长奖-青光眼是全球的一个主要问题，目前有6000万人受到影响，其中112人 预计到2040年将达到100万。目前，青光眼的主要治疗方法依赖于 外用滴眼液，与前列腺素类似物，作为一线治疗，占总处方的51%。 然而，由于泪液引流，滴眼液的生物利用度受到很大限制，而患者情况较差。 在每日滴注养生法的患者中，依从率为50%。二线投放需要更频繁的投放 每天给药，因此对治疗的依从性更差。我们建议开发一种药物递送装置 可延长配戴时间并可持续释药长达7天的隐形眼镜(DDCL)，用于治疗开放性黄斑变性 房角青光眼。其目标是取代局部滴眼液作为青光眼护理的标准。主要优势 DDCL的特点是剂量频率较低，以恒定的速度直接输送到角膜表面， 精确的剂量和靶向，所有这些都由一个具有成本竞争力的镜头设备完成。拟议的第二阶段工作计划将侧重于 精制DDCL原型(包括药物释放、材料等)，扩大生产规模，以及 在耐受性、药代动力学和药效学的动物模型研究中证明了可行性。这个 提出的DDCL不仅解决了滴眼剂的所有不足之处，而且可能会建立一个新的 与眼部绷带、可注射聚合物、外科植入物等其他竞争技术的标准。 在以下类别中：(A)药物释放速率的精确控制在一级至零级动力学之间 在整个给药期间，(B)根据匹配率精确配给生物可用药量 药物释放、泪液周转和角膜吸附；(C)配戴7天所需的镜片材料创新 舒适、安全、易于操作(由老年人)，而且价格具有竞争力。在第二阶段结束时，最终生产- 动物可行性数据(63只兔，毒性/PK/PD)的规模原型将准备好用于后续的IND- 如即将到来的第二阶段项目所建议的那样，使研究和IND申请用于人体研究。 行政补编--本行政补编提议增加预算费用168,192美元 完成之前计划与一所大学(坦普尔)合作的分奖动物研究，但由于时间的原因， 人员和其他限制已转移到CRO(ORA Inc.)。研究设计保持不变， 唯一的变化是分获奖者、设施和预算，将允许及时完成工作。 更新的IACUC批准和OLAW保证已经完成。

PROJECT SUMMARY Parent award – Glaucoma is a major problem worldwide, with 60 million people currently affected and 112 million expected by 2040. At present, the primary treatment of glaucoma relies on medication administered as topical eye drops, with prostaglandin analogues, as the first-line therapy, representing 51% of total prescriptions. However, eye drops present significant limitations in bioavailability due to tear drainage, and a poor patient adherence rate of 50% amongst those with a daily drop regimen. Second-line drops require even more frequent dosing per day and hence worse adherence to the therapy is observed. We propose to develop a drug-delivering contact lens (DDCL) with extended wear and sustained drug release of up to 7 days for the treatment of open- angle glaucoma. The goal is to replace topical eye drops as the standard of care for glaucoma. Key advantages of the DDCL will be lower dosing frequency, direct delivery to the corneal surface at a constant rate, high- precision dosing and targeting, all by a cost-competitive lens device. The proposed Phase II work plan will focus on refining prototypes of the DDCL (including drug release, materials, etc.), scaling up the production, and demonstrating feasibility in animal model studies of tolerability, pharmacokinetics and pharmacodynamics. The proposed DDCL will not only resolve all the deficiencies of eye drop administration, but also could set a new standard against other competing technologies of ocular bandages, injectable polymers, surgical implants, etc. in the following categories: (a) The accurate control of drug release rate between first to zero order kinetics throughout the delivery duration, (b) The precise dosing of bioavailable drug amount based on matching rates of drug discharge, tear turnover and corneal adsorption, (c) The lens material innovation required for 7-day wearing comfort, safety, easy of handling (by elderlies), and at a competitive cost. At the end of Phase II, final production- scale prototypes with animal feasibility data (63 rabbits, toxicity/PK/PD) will be ready for subsequent IND- enabling studies and IND filing for study in humans as proposed in an upcoming Phase IIb project. Administrative supplement – This administrative supplement proposes $168,192 of incremental budget costs to complete subaward animal research that was previously planned with a university (Temple), but due to timing, personnel and other constraints has been moved to a CRO (Ora Inc.). The study design remains the same, with the only changes being the subawardee, facility, and budget that will allow for timely completion of the work. Updated IACUC approval and OLAW assurance have already been completed.