Structure-property relationships in poly(pro-17-estradiol) materials and the effect on in vitro degradation kinetics

Abstract

Due to the refractory nature of the central nervous system (CNS), injuries such as spinal cord injury (SCI) trigger a complex injury cascade. Currently, no effective therapeutics exist to reverse the outcomes of progressive secondary injuries caused by SCI. The debilitating, long-term effects of SCI have created the need for a controlled extended-release drug delivery platform. 17-Estradiol (E2) is known to have neuroprotective, neurotrophic, and immunosuppressive properties making it a promising therapeutic for CNS injuries. The central motivation of this work is to examine structure-property relationships in polymerized estrogen materials to create tunable material properties and release kinetics. The design, testing, and characterization of poly(pro-E2) biomaterial scaffolds is reported and presents a promising drug delivery platform to target CNS injuries. The strategies employed in the synthesis of the library of poly(ester) and poly(carbonate) E2 prodrugs with varying chain modifiers presented is highly applicable to other polymer classes leaving limitless possibilities to tailor material properties and control drug release kinetics.