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

SBIR 第二阶段：水凝胶的受控药物释放和降解

• 批准号: 1429972
• 负责人: Gary Ashley
• 金额: $ 74.28万
• 依托单位: ProLynx LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-11-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1429972&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Controlled; Drug

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.

这项小型企业创新研究（SBIR）I期项目的更广泛的影响/商业潜力是通过改进的医疗治疗方法改善公共卫生和生活质量。该项目开发的技术旨在提高现有治疗药物的有效性，同时支持需要治疗的患者使用，并能够发展承诺新的治疗剂和机构，否则由于其管理的要求或复杂性而无法有用。例如，如果成功的话，该技术将服用需要每日注射（或每天多次注射）的药物，并将其转换为只需要每周一次注射的表格。预期的社会影响会增加患者的依从性，并提高治疗的有效性，从而总体上改善患者生活质量。预计将现有治疗方案替换为更方便，更有效的治疗方案将产生重大的商业影响，使新的治疗疗法也可以治疗当前未经处理或无效治疗的状况的新疗法。拟议项目旨在基于对药物的受控释放，尤其是Pepperides和Proteins的释放，旨在开发一种平台技术，尤其是从注射剂中。当前方法由于其制造方式或化学反应性而与辣椒和蛋白质不兼容，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容易注入的可生物降解水凝胶基质，该水凝胶基质以高度控制的方式释放出绑定的药物，然后以高度控制的方式溶解。水凝胶基质提供了一种蛋白质友好的环境，使用？脱离的接头可导致释放和降解动力学的精确控制。技术开发将集中于普通肽/蛋白质的药物附着物质以及水凝胶基质本身的化学，但将使用特定的治疗应用（例如Exenatide和GLP-1）进行例证，例如立即应用于2型糖尿病和肥胖症的治疗。同时将开发用于水凝胶行为的体内分析的方法，并将评估水凝胶基质的耐受性。