SBIR Phase I: Hyaluronan-Based Ocular Delivery of Antibiotics

SBIR 第一阶段：基于透明质酸的抗生素眼部递送

• 批准号: 1315150
• 负责人: Barbara Wirostko
• 金额: $ 15万
• 依托单位: Jade Therapeutics
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1315150&HistoricalAwards=false
• 关键词: SBIR; Phase; Hyaluronan; Based; Ocular

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.

这个小企业创新研究第一阶段项目评估了使用一种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，该产品可以在延长的每周周期内直接、局部和连续地将抗生素输送到眼表。这片结合了促愈合，抗炎作用的透明质酸和缓慢释放的眼科抗生素。眼用局部抗生素需要频繁给药（即角膜溃疡每小时一次），这往往导致给药不当，导致眼睛的生物利用度不理想和大量浪费。这种新型聚合物薄膜可以局部放置在眼表面，以传递一种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原型膜，并对膜降解、抗菌功效和药物释放进行评估。含抗生素薄膜的安全性和耐受性将在临床前兔模型中进行验证。我们期望能够生产出耐受性良好的抗生素释放膜产品原型，并展示所需的特性。这样的膜将允许我们进展到II期SBIR，以优化无菌和临床有用的商业产品。该项目的更广泛的影响/商业潜力是开发一种新的眼部药物输送产品，通过提供一种更高效、有效、方便和一致的抗生素直接输送到眼表的方法来改善患者护理。使用已知的具有内在愈合特性的聚合物载体，该产品将在局部提供连续足够的剂量，从而消除了频繁的局部（每小时）和/或全身剂量的抗生素，用于广泛的感染性眼病。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。相关眼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。这种局部延长释放产品通过提供医疗保健提供者放置的抗生素产品急性管理，解决了军队和平民人口中重要的未满足的医疗需求。在第一阶段生产和评估的含抗生素薄膜最终会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，通过展示多碱抗生素的释放，这种系统可以扩展到提供其他抗微生物药物来治疗眼部真菌或病毒感染，这在发展中国家是一项重大挑战。