Therapeutic Platform for Hypothermia Induction following Traumatic Brain Injury

Project: Research project

Project Details

Description

PROJECT ABSTRACT We propose the development and testing of an innovative platform based on carrier-free nanomaterials that are solely derived from pharmaceutical drugs, for application in localized and targeted therapeutic hypothermia (TH). TH application has gained interest in the medical field as a useful treatment for protecting nervous tissues from secondary injury mechanisms after various neurological disorders. This experimental therapy is based on intentionally decreasing the core body temperature to prevent a surge in neuronal cell death. The current clinical status of TH remains under investigation with several factors including patient selection, therapeutic window, and optimal temperature levels still to be determined. An alternative to induced hypothermia is a pharmacological approach although current investigations of drug-induced hypothermia can be associated with several drawbacks, such as the use of high doses of the drugs/agents, the intravenous route of administration, slow induction of TH, and multiple side effects. Therefore, we propose to develop and test novel nanomaterials made of drugs, i.e., nanodrugs, to address the technical and medical challenges related to efficiency, speed, and minimization or absence of toxicity and side effects. Nanodrugs with cooling properties will be prepared using non-toxic vanilloid compounds (nano-vanilloids), including natural compounds; these formulations will be administered as a useful treatment to secure neuroprotection. Nano- vanilloids are made of vanilloid molecules assemblies at the nanoscale to exhibit enhanced intrinsic therapeutic properties related to the original parent vanilloid drug. The importance of the proposed nanoscale formulations is their high efficiency to induce TH; therefore, only a small dosage is required to achieve the target temperature, which underlines the safety and tolerability of these developed platforms. The nanodrugs will also offer a longer bioavailability in comparison to the original vanilloid molecules, thus, avoiding the need for frequent dosing. The synthesis of nano-vanilloids is performed using bottom-up approaches, and these nanodrugs will be locally delivered via a nasal spray to target a thermoregulatory receptor located in the brain, contributing to a quick induction of TH. Characterization and optimization of the nanodrugs will be performed with regard to controlling their size and stability to secure an efficient performance of targeted hypothermia in vitro and in vivo. To evaluate the ability of nanodrugs to effectively induce hypothermia and produce neuroprotection, we will use an established TBI model that has previously been shown to be sensitive to TH. We believe that this research represents nanotechnology-based advances in the fields of nanomaterials design and preparation, drug delivery, and hypothermia therapies, which should have a significant impact in the rapid treatment and prevention of permanent damage in patients caused by TBI, as well as other clinical conditions.
StatusActive
Effective start/end date9/30/208/31/22

Funding

  • National Institute of Neurological Disorders and Stroke: $422,125.00

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