SBIR Phase I: Hyaluronan-Based Ocular Delivery of Antibiotics

该小型企业创新研究I期项目评估了使用基于改性生物聚合物水凝胶的新型协同药物-聚合物眼膜产品的可行性，以在延长的每周时间内将抗生素直接，局部和连续地递送到眼表。这部电影结合了促愈合，抗炎作用的透明质酸与缓慢释放的眼科抗生素。局部眼部抗生素需要频繁给药（即，对于角膜溃疡，每小时一次），经常导致不适当的给药，导致眼睛的次优生物利用度和相当大的浪费。这种新型聚合物膜可以局部放置在眼表上以递送众所周知的眼科抗生素。 我们建议通过提供抗生素来扩大局部水凝胶的已知益处，以减少局部细菌感染，同时加速和改善愈合。将生产含有抗生素的水凝胶的原型膜，并评价膜降解、抗菌功效和药物释放。将在临床前兔模型中证明含维生素C的膜的安全性和耐受性。我们期望能够生产出耐受性良好的药物释放膜产品原型，并展示出所需的特性。这样的薄膜将使我们能够进入第二阶段SBIR，以优化无菌和临床上有用的商业产品。该项目更广泛的影响/商业潜力是开发一种新的眼部药物递送产品，通过提供更有效，更有效，更方便，更一致的方式将抗生素直接递送到眼表，从而改善患者护理。使用具有内在愈合特性的已知聚合物载体，该产品将局部递送连续的足够剂量，从而消除了用于广泛的感染性眼科病症的频繁的局部（高达每小时）和/或全身剂量的抗生素。这提高了患者的依从性和患者的治疗效果，同时降低了医疗保健成本。相关的眼部疾病包括角膜和结膜的活动性感染，以及预防与各种眼部手术和疾病相关的潜在感染。这种局部缓释产品通过提供医疗保健提供者放置的抗生素产品急性给药，解决了军队和平民群体中重要的未满足的医疗需求。在阶段I中生产和评价的含抗生素的膜最终可以导致商业上可行的眼部护理产品的开发，以解决这些未满足的需求。此外，通过证明多元抗生素的释放，这种系统可以扩展到提供其他抗菌剂来治疗眼部真菌或病毒感染，这在发展中国家代表着重大挑战。

This Small Business Innovation Research Phase I project assesses the feasibility of using a novel synergistic drug-polymer ocular film product based on a modified biopolymer hydrogel to deliver antibiotics directly, locally and continuously to the ocular surface over an extended weekly period. This film combines the pro-healing, anti-inflammatory effects hyaluronic acid with slow release of an ophthalmic antibiotic. Topical ocular antibiotics require frequent dosing (i.e., hourly for corneal ulcers), often resulting in improper administration, causing suboptimal bioavailability to the eye and considerable waste. This novel polymer film can be placed on the ocular surface topically to deliver a well-known ophthalmic antibiotic. We propose to expand on known benefits of topical hydrogels by delivering antibiotics to reduce bacterial infections locally while simultaneously accelerating and improving healing. Prototype films of hydrogel containing antibiotics will be produced and evaluated for film degradation, anti-bacterial efficacy, and drug release. Safety and tolerability of the antibiotic-containing films will be demonstrated in a preclinical rabbit model. We anticipate being able to produce a well-tolerated antibiotic-releasing film product prototype and demonstrate the desired characteristics. Such a film would allow us to progress to a Phase II SBIR to optimize a sterile and clinically useful commercial product.The broader impact/commercial potential of this project is development of a new ocular drug delivery product that will improve patient care by providing a more efficient, effective, convenient, and consistent means of antibiotic delivery directly to the ocular surface. Using a known polymer carrier with intrinsic healing properties, this product will deliver continuous adequate doses locally, thus eliminating the frequent topical (up to every hour) and/or systemic doses of antibiotics for a wide range of infectious ophthalmic conditions. This improves patient compliance and patient outcomes, while reducing health care costs. Relevant eye diseases include active infections of the cornea and conjunctiva, as well as prevention of potential infections associated with various ocular surgeries and diseases. This topical extended release product addresses important unmet medical needs in the military and in civilian populations by providing healthcare provider-placed antibiotic product administered acutely. The antibiotic-containing films produced and evaluated in Phase I can ultimately lead to the development of a commercially viable ocular care product to address these unmet needs. Further, by demonstrating release of polybasic antibiotics, such a system could be expanded to deliver other antimicrobials to treat ophthalmic fungal or viral infections, which represent significant challenges in developing countries.