Dr. Belinda Akpa receives a NSF grant entitled, "BRIGE: Colloidal scavengers for the reversal of drug toxicity". It provides $175,000 over 2 years.
Fatalities due to drug intoxication occur frequently and their incidence is on the rise (145% increase in the 8 year period from 1999-2007). Sudden death following poisoning is second only to motor vehicle accidents in causing fatalities within the category of death due to unintentional injury. The vast majority of these unintentional poisonings (93%) are due to drug intoxication and the most frequent culprits are prescription drugs. Most life-threatening intoxicants do not have a specific pharmacological antidote. As the incidence of unintentional poisonings continues to rise, there is clearly a need to develop treatment modalities that mitigate the acute effects of toxic drug concentrations. The case of local anesthetic overdose has presented a possible "silver bullet" for the treatment of drug overdoses that are unresponsive to standard resuscitation measures. Intravenous oil-in-water formulations, commonly used in hospitals as a source of IV nutrition, have the potential to resuscitate patients suffering cardiac arrest due to otherwise fatal poisonings. The objective of this proposal is to identify the factors that determine successful coupling of a lipid emulsion formulation and a target toxin for the purposes of reducing tissue exposure to drugs and, consequently, facilitating resuscitation following drug overdose. In vitro measures of drug-lipid binding characteristics will be combined with macroscale models of physiological drug distribution and molecular scale studies of drug-lipid layer interactions to comprehensively probe the potential of a lipid scavenger to reverse the accumulation of toxins in cardiac tissues.
An improved understanding of the nature non-specific binding of lipophilic molecules with (or transport through) phospholipid layers may be used to develop colloidal formulations specific to scavenging applications. It is
anticipated that a successful non-specific colloidal scavenger -- particularly a highly biocompatible one -- will have broad impacts. Such an agent could, for example, be exploited as a potential means of reversing toxicity due to chemical warfare agents such as organophosphates. These same compounds are also used as pesticides and, in developing nations, are
frequent culprits in intentional and accidental poisonings. Furthermore, there is significant interest in employing lipid droplets as vehicles for biocompatible delivery of poorly water-soluble compounds.