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DELIVERY OF NEUREGULIN-1 THROUGH AN OSMOTIC TRANSPORT DEVICE (OTD)

Abstract

In traumatic brain injury (TBI), secondary injury involving neurological damage andedema negatively impacts recovery outcomes. Previous studies have shown that an osmotictransport device (OTD) significantly decreases severe TBI edema in rodent models. Because theOTD requires a craniectomy for direct contact to the brain, it is expected that the simultaneousdelivery of the neuroprotective drug, neuregulin-1 (NRG-1), may further improve neurologicaloutcomes. However, the release rate of NRG-1 must be controlled. In addition, becausehydrogel-drug interactions can be highly complex and impact overall delivery, the release ofNRG-1 from hydrogel must be analyzed. Previous research has shown that hydroxyethylcellulose (HEC) may have the appropriate properties for this purpose. Here we test the release ofthe active EGF-like domain of NRG-1 from a hydrogel made up of 1.5%, 2.0%, and 2.5% HECand artificial cerebrospinal fluid. Concentrations of the EGF domain are measured via anenzyme-linked immunosorbent assay. The results show concentration dependent Fickiandiffusion behavior, with 2.0% HEC being the most promising of the hydrogels tested.Ultimately, the controlled delivery of NRG-1 integrated with an OTD will greatly improverecovery outcomes for victims of severe TBI.

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