Biointerfacing Polymers to Overcome Challenges in Vaccine Delivery, Gene Therapy, and Cancer Therapy

Abstract

Polymers can be designed to interface with biological entities, including biological molecules, cells, and tissues, and to modulate their properties and behaviors. In this dissertation, biointerfacing polymers were used to overcome four key challenges in vaccine delivery, gene therapy, and cancer therapy. First, mucoadhesive wafers composed of binary polymer blends of carboxymethylcellulose and alginate were developed to preserve the activity and improve the sublingual delivery of protein vaccines. Second, polymer wafers composed of polyvinyl alcohol were developed to enhance polyplex-mediated gene transfection in vitro in the presence of serum. Third, a synthetic membranolytic polymer poly(6-amino-1-hexyl methacrylate) (PAHM) was used to disrupt cancer cell membrane, resulting in increased cellular uptake of doxorubicin and synergistic killing of cancer cells. Finally, PAHM was used to sensitize cancer cells to irreversible electroporation (IRE), leading to enhanced killing at electric field strengths lower than IRE alone. These studies have laid the foundation for future development of new and transformative medical technologies.