ABSTRACT

PI: Akpa
Proposal Number: 1228035

Intellectual Merit Fatalities due to drug intoxication occur frequently and their incidence rose 145% 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.

Scientific Broader Impacts 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.

Broadening participation: The proposed Science Siblings (S2) program is a multi-level mentoring initiative. The program will emphasize the positive role engineers play in addressing society's greatest challenges as a pathway to attracting under-represented groups into engineering disciplines. Both women and minorities often consider the impact their career choice will have on their communities when making education and career decisions. S2 aims to impact awareness of engineering as a multi-faceted, socially impactful profession amongst participants from the high school to the graduate level. Participants will include the PI as a leader or parent, graduate students as elder siblings, and undergraduate students as younger siblings (engineering students at UIC and science students from local community colleges). The S2 family will also include K-12 teachers who will act as pedagogy advisors regarding the integration of our planned Engineer in Society project modules with Illinois Learning Standards for Science. Each group has a place in the hierarchy that corresponds to different responsibilities. The structure will provide opportunities both for downward mentoring and for peer-to-peer mentoring and should lead to the feeling of "connectedness" that has been shown to be important in student retention.

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