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

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.