SBIR Phase I: A Universal Drug Delivery System for Wet Epithelia

这个SBIR一期项目的更广泛/商业影响旨在使生物制剂的使用成为可能，生物制剂是一类更新的药物，由于其显着的有效性和特异性而转化为药物，用于治疗身体潮湿表面的疾病。许多疾病发生在身体潮湿的表面，包括口腔、关节、肺和胃肠道。这些地区目前没有局部应用生物制剂，因为这些药物在产生任何益处之前就会迅速被冲走。生物制剂有时通过输注来治疗这些疾病，但这有严重甚至危及生命的副作用的风险。如果生物制剂可以局部使用，副作用就会少得多，而且在潮湿的表面上治疗疾病也会比目前可能的更积极、更有效。该项目的成功完成将为该技术建立概念验证，并创建一个新的平台，以以前不可能的方式治疗这些疾病，造福患者。该公司将与制药合作伙伴公司合作，利用其综合资源将这些产品商业化并改善健康结果。其核心思想是将生物制剂固定在潮湿的表面，使其作用时间更长（数小时或数天）。延长给药时间的传统方法使用某种形式的有问题的载体；大多数不能与生物制剂一起使用。该项目将在小鼠模型上验证该技术对普通干眼病的治疗效果。抗体是迄今为止最大的一类生物制剂，并且已经开发出一种将锚点附着在抗体上同时保持其活性的程序。这项研究的目的是验证：1)附着一个锚点可以延长抗体在角膜上停留的时间。在角膜表面的停留时间将用荧光标记抗体测量，有或没有锚点。2)锚定抗炎抗体是治疗干眼症的有效药物。将确定用带锚点和不带锚点的抗体治疗小鼠对干眼病严重程度的影响。这些目标将测试一个假设，即在生物上附着一个锚可以增加其停留时间和治疗效率，从而提供概念证明。没有其他公开已知的方法，以这种方式解决药物冲洗问题，以治疗干眼病存在。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader/commercial impact of this SBIR phase I project aims to enable the use of biologics, a newer class of drugs transforming medicine due to its marked effectiveness and specificity, to treat diseases at wet surfaces of the body. Many diseases occur at wet surfaces in the body including the oral cavity, joints, lungs, and gastrointestinal tract. Local application of biologics is currently not used in these areas because the drugs are rapidly washed away before they have any benefit. Biologics are sometimes administered by infusion to treat these diseases, but this has risks of serious, even life-threatening side effects. If biologics could instead be delivered locally, side-effects would be much less of a concern and diseases at wet surfaces could be treated more aggressively and effectively than currently possible. Successful completion of the project will establish proof-of-concept for the technology and create a new platform to treat these diseases to the benefit of patients in ways that were previously impossible. The company will work with pharmaceutical partner companies to utilize their combined resources to commercialize these products and improve health outcomes.The central idea is to anchor biologics to wet surfaces so that they act for longer periods (hours or days). Traditional approaches to prolonged drug delivery use some form of problematic carrier; most cannot be used with biologics. The project will validate the technology as a treatment for common dry eye disease, using a mouse model. Antibodies are by far the largest class of biologics, and a procedure has been developed to attach anchors to antibodies while maintaining their activity. The research aims are to validate that: 1) Attaching an anchor prolongs the time an antibody resides on the cornea. The residency time on the corneal surface will be measured using fluorescently labeled antibodies with and without an anchor. 2) An anchored anti-inflammatory antibody is an effective drug to treat dry eye. The effects on the severity of dry eye disease by treating mice with antibodies with and without an anchor will be determined. These aims will test the hypothesis that attaching an anchor to a biologic increases its residency time and its therapeutic efficiency providing proof-of-concept. No other publicly known method of solving the drug washout problem in this manner to treat dry eye disease exists.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.