SBIR Phase II: Controlled Drug Release from and Degradation of Hydrogels

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是通过改进药物治疗方法来改善公众健康和生活质量。 该项目开发的技术旨在提高现有治疗药物的有效性，同时促进需要治疗的患者使用这些药物，并开发有前途的新治疗药物和方案，否则由于其给药的频率或复杂性而无法使用。 例如，如果成功，该技术将采用需要每天注射（或每天多次注射）的药物，并将其转化为只需每周注射一次的形式。 预期的社会影响是增加患者依从性以及治疗有效性的改善，从而整体改善患者的生活质量。 用更方便和有效的治疗方案取代现有的治疗方案预计将产生巨大的商业影响，因为新的治疗方法能够治疗目前未治疗或治疗无效的疾病。拟议的项目旨在开发一种基于药物，特别是肽和蛋白质从注射贮库中控制释放的平台技术。 目前的方法或者由于肽和蛋白质的制造模式或化学反应性而与肽和蛋白质不相容，或者不提供对最佳治疗效率所需的释放和降解速率的精确控制。所提出的方法将开发一种可生物降解的水凝胶基质，其易于注射，以高度受控的方式释放结合的药物，并且随后以高度受控的方式溶解。 水凝胶基质提供了一个蛋白质友好的环境，和使用？β-消除连接子导致释放和降解动力学的精确控制。技术开发将集中于一般化肽/蛋白质的药物附着化学以及水凝胶基质本身的化学，但将使用具有现有治疗应用的特定治疗肽来举例说明，例如立即适用于治疗2型糖尿病和肥胖症的艾塞那肽和GLP-1。 同时，将开发水凝胶行为的体内分析方法，并评估水凝胶基质的耐受性。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is an improvement in public health and quality of life through improved methods of medicinal therapy. The technology developed in this project is aimed at improving the effectiveness of existing therapeutic drugs while facilitating their use by patients in need of treatment, as well as enabling the development of promising new therapeutic agents and regiments that otherwise would not be useful due to the required frequency or complexity of their administration. As an example, if successful this technology will take a drug requiring daily injection (or multiple injections every day) and convert it to a form that requires injection only once-weekly. The anticipated societal impact is increased patient compliance together with an improvement in the effectiveness of the treatment, and thus an overall improvement in patient quality of life. The replacement of existing treatment regimens by more convenient and effective ones is expected to have a substantial commercial impact, as is the enablement of new therapeutics to treat currently untreated or ineffectively-treated conditions.The proposed project is aimed at developing a platform technology based on the controlled release of drugs, particularly peptides and proteins, from an injected depot. Current methods are either incompatible with peptides and proteins due to their mode of manufacture or chemical reactivity, or do not provide the precise control over release and degradation rates that are needed for optimum therapeutic efficiency. The methods proposed will develop a biodegradable hydrogel matrix that is readily injected, that releases a bound drug in a highly controlled manner, and which subsequently dissolves in a highly controlled manner. The hydrogel matrix provides a protein-friendly environment, and use of ?Ò-eliminative linkers results in precise control of release and degradation kinetics. Technology development will be focused on the chemistry of drug attachment for generalized peptides/proteins as well as the chemistry for the hydrogel matrix itself, but will be exemplified using specific therapeutic peptides having existing therapeutic applications, such as exenatide and GLP-1 that are of immediate applicability to the treatment of Type 2 diabetes and obesity. Concomitantly, methods for the in vivo analysis of hydrogel behavior will be developed, and tolerability of the hydrogel matrix will be assessed.