(17a) Core Crosslinked Nanoparticles for Treating Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of disability and death in people under 45. Following the primary insult of a TBI, secondary injury caused in part by the spread of reactive oxygen species (ROS) into surrounding normal brain can lead to lifelong neurocognitive, physical, and psychosocial impairments. There are currently no treatments available that have shown improved efficacy in a large Phase III trial. We have developed oxygen reactive polymer, core crosslinked nanoparticles that can bind and inactivate ROS in the thioether core. These nanoparticles can rapidly accumulate and be retained in damaged brain in a controlled cortical impact mouse model of TBI. Treatment with the nanoparticles resulted in reduced spread of secondary injury in these mice as determined by magnetic resonance imaging and histopathological analyses. Importantly, mice that received nanoparticle treatment performed better in the startle habituation test of learning suggesting improved neurocognitive function. Our findings show these nanoparticles may provide an effective therapy for reducing secondary injury following a TBI.