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

小型企业创新研究(SBIR)第一阶段项目的更广泛影响/商业潜力是通过改进药物治疗方法改善公共卫生和生活质量。在这个项目中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，并使有希望的新治疗药物和药物的开发成为可能，否则由于给药的频率或复杂性，这些药物将毫无用处。例如，如果成功，这项技术将接受需要每天注射(或每天多次注射)的药物，并将其转换为每周只需注射一次的形式。预期的社会影响是增加患者的依从性，同时改善治疗的有效性，从而全面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重大的商业影响，使新的疗法能够治疗目前未经治疗或治疗无效的疾病。拟议的项目旨在开发一种基于从注射库控制药物释放的平台技术，特别是多肽和蛋白质。目前的方法要么由于制造方式或化学反应能力而与多肽和蛋白质不兼容，要么不能精确控制释放和降解率，而这是最佳治疗效率所需的。所提出的方法将开发一种易于注射、以高度受控的方式释放结合药物并随后以高度受控的方式溶解的生物可降解水凝胶基质。水凝胶基质提供了对蛋白质友好的环境，使用消除连接物可以精确控制释放和降解动力学。技术开发将侧重于一般多肽/蛋白质的药物结合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多肽作为例证，例如立即适用于治疗2型糖尿病和肥胖症的埃克塞那肽和GLP-1。与此同时，将开发水凝胶行为的体内分析方法，并将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.