Date of Graduation

5-2015

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Zaharoff, David A.

Abstract

Controlled and localized delivery of Interleukin 12 (IL-12) is critical to effective and non-toxic cancer immunotherapy. Current delivery protocols for pre-clinical anti-tumor trials utilize solutions of chitosan, a mucoadhesive and bioeliminable biopolymer, to slow the release of IL- 12 into the tumor microenvironment. In order to further increase IL-12 retention, we have developed and characterized two chitosan-based in situ gelling hydrogels for IL-12 immunotherapy. One hydrogel, composed of heparin and chitosan, is herein described from initial conception through multiple stages of characterization including isolation of a range of suitable hydrogel formulations and observational physical and chemical properties. A second hydrogel is primarily composed of modified chitosan polymer. This hydrogel was characterized in previous studies, but the release kinetics (in vitro and in vivo) were not defined. In order to better understand this hydrogel, we performed both in vitro and in vivo protein release studies that validate this platform as a candidate for improved IL-12 therapy. Results indicate that the hydrogel and modified chitosan solution elicit protein retention at least twice as well as the chitosan solution currently used. Future studies will further examine release kinetics of the heparin-chitosan hydrogel and the anti-tumor response in mouse models using both hydrogels. If successful, these IL-12/hydrogel formulations will provide new clinical treatments for patients with solid tumors.

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