Polyvinyl alcohol-polyvinyl pyrrolidone thin films provide local short-term release of anti-inflammatory agents post spinal cord injury

Abstract

Spinal cord injury (SCI) triggers a large inflammatory response that results in exacerbated tissue damage. Locally delivering anti-inflammatory drugs could mitigate this secondary wave of degeneration. The mitogen-activated protein kinase family members p38 and c-Jun N-terminal kinase (JNK) play important roles in the inflammatory response and cell death. We propose that the use of polymer thin films, made of polyvinyl alcohol and polyvinyl pyrrolidone blends (PVA-PVP), can be used to provide local release of inhibitors to p38 and JNK post-SCI. Release studies performed in vitro confirmed the inhibitors could be released from the film for up to 7 days. The thin film was also tested for its surgical feasibility using a cervical contusion model of SCI in adult female rats. Films with or without the inhibitors were placed subdurally over the injury site immediately following SCI. Animals were sacrificed 5 days post-SCI and spinal cord tissue above and below the injury site was harvested. Additionally, films were removed for analysis. Scanning electron microscopy confirmed the anti-fouling properties of the PVA-PVP film. Tissue histology confirmed that the films themselves did not generate a large immune response, but they did compress the tissue slightly at its placement above the injury site. Finally, quantitative Western blot analysis determined the films loaded with p38 and JNK inhibitors delivered bioactive agents to the injury site and resulted in a significantly decreased amount of pro-cell death proteins. These data indicate that PVA-PVP films can be used to effectively deliver drugs to a SCI site.