Poster N11 - Development and characterization of poly(pro-E2) films for sustained drug release in spinal cord injury applications

Introduction: Many studies have shown that 17β-estradiol (E2) possesses neuroprotective and anti-inflammatory properties. E2 can also be chemically modified into a prodrug, to increase bioavailability and its subsequent scope of applications. Incorporation of E2 into a poly(prodrug) was executed to create a biomaterial capable of undergoing sustained drug release. A polymerized prodrug of E2, poly(pro-E2) was synthesized, in which E2 is a component of the polymer backbone which can be released as the active drug upon hydrolysis. This material could have a variety of applications, and this research focuses on using it to negate the detrimental effects of the secondary injury response of spinal cord injury, which can be prolonged for months to years after the initial trauma.

Materials and

Methods: In this research, three types of poly(pro-E2) polymers differing in their chemical structure were characterized. These polymers vary in their carbon chain length, containing a single saturated 3, 6, or 9–carbon chain in the backbone. It was hypothesized that the addition of longer flexible chains would increase the polymer’s flexibility and would subsequently undergo faster release kinetics.

A variety of characterization techniques were used to determine the mechanical properties, thermal properties, and release kinetics of the polymers, including: nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), goniometry, and liquid chromatography mass spectrometry (LCMS).

Results, Conclusions, and Discussions: In this work, we evaluated the three poly(pro-E2) variants for their mechanical and thermal properties. Additionally, we quantified the degradation and release rates between them and correlated these rates with the physical properties previously determined. NMR and GPC were employed to confirm the extent of polymerization and determine molecular weight distribution of each batch. To characterize their thermal properties, DSC was utilized to determine glass transition temperature (Tg) which can distinguish between hard, rigid and soft, flexible polymers, and is indicative of polymer mechanical properties as well. DMA confirmed the results obtained by DSC, that the 9-carbon linker polymers (PE-C9) indeed exhibit greater flexibility, although they undergo slower degradation and release, as seen through LCMS measurements. This may be due to the presence of more hydrophobic carbon atoms in the longer chains increasing hydrophobicity of the polymer (which was measured with goniometry). This creates decreased ability to take in water and slows hydrolysis of the polymer backbone. Ultimately, this work aims to develop a biomaterial capable of demonstrating slow, sustained, localized release of a neuroprotective and neurotrophic drug that can be utilized in SCI recovery and various other neural injury and disease systems.

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