DURIP Liposomal antioxidant therapies for mitigation of CNS oxygen toxicity
Abstract
This equipment proposal requests funds to procure new instrumentation for producing solutions in our laboratory of lipid-encased nanoparticles containing antioxidative molecules. These so-called liposomal-antioxidants and lipid nanoparticle-antioxidants will be tested in an established small animal model (rat) of CNS oxygen toxicity (CNS-OT) during exposure to hyperbaric oxygen with/without CO2 retention (HBO2 # CO2). Our working hypothesis is that lipid-encapsulated antioxidants administered systemically via the noninvasive intranasal route will have improved bioavailability to neurons and synapses due to better penetration through the blood brain barrier and delayed metabolism of the active #cargo#, i.e., antioxidants. The net effect will be greater neuroprotection against CNS-OT#i.e., delayed or potentially blocked seizures#for safer, longer operational dives when breathing HBO2. In addition, funds are also requested to purchase hardware and software upgrades for our existing hyperbaric radio telemetry system, which was originally purchased in 2010 using ONR funds. Radio telemetry is used to monitor brainwaves (electrical seizure activity) that occur in tandem with visible motor seizures in unanesthetized, freely behaving rats. Recall that generalized cortico-motor seizures are the main sign of CNS-OT caused by breathing HBO2. The latency time to seizure onset is how we quantify sensitivity of the animal to HBO2 and the effectiveness (or lack thereof) of a given liposomal antioxidant. Thus, the equipment requested will be used as one system in that it permits us to i) synthesize liposomal and lipid nanoparticle-encapsulated antioxidants (NanoGenerator ProTM) and then ii) test their ability to delay seizure genesis in rats by measuring cortico-motor seizures (DSI radio telemetry system upgrade and replacement telemetry modules).Our planned experiments will focus on antioxidants using the following criteria: i) the antioxidant to be tested has good potential for delaying seizures during exposure to HBO2 based on critical analysis of the literature; and ii) the antioxidant in question has a strong likelihood of being approved for use in human if it#s an effective inhibitor of CNS-OT in rats. The equipment requested in the proposal is anticipated to be used by postdoctoral or graduate student scientists who train in the P.I.#s laboratory, other DOD performers at USF, and scientists affiliated with the DoD/ONR Undersea Medicine Program who visit the P.I.#s laboratory. Thus, we expect that multiple military-related scientists, will benefit from having access to this new equipment for generating liposomal nanoparticles.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 15, 2024
- Source ID
- N000142412251
Entities
People
- Jay B. Dean
Organizations
- Office of Naval Research
- United States Navy
- University of South Florida