Abstract: High precision pharmacokinetic measurements in brain using a novel aptamer-based biosensor DESCRIPTION The addiction potential of a drug is related to the rate at which it interacts with the brain. Drug abuse is particularly problematic for prescribed therapeutic drugs as they are a major contributor to the current addiction epidemic. In order to increase drug efficacy and mitigate toxicity, it is crucial to monitor drug pharmacokinetics. Traditional methods for monitoring drug pharmacokinetics require the removal of samples from the brain by microdialysis for later analysis in the laboratory, rendering them slow and cumbersome and greatly limiting their temporal resolution. In contrast, the development of a novel electrochemical aptamer-based (E-AB) biosensor by the mentor's group has opened the door for the continuous, ultra-high-resolution monitoring of drugs in living subjects. For example, the PI has already used this technology to measure multiple drug targets, demonstrating accurate, high-precision (seconds-resolved) pharmacokinetic tracking of these compounds over multiple hours in a live animal model. To expand this promising platform for understanding drug metabolism, the PI will apply it to characterizing the pharmacokinetics of compounds that cross the blood-brain barrier (BBB). These will include the prescription opioid oxycodone and the addictive illicit drug cocaine. Here, the PI intends to implement E-AB sensors to measure the real-time pharmacokinetics these compounds in brain, thus not only improving our understanding of the time course of drugs crossing the BBB, but to also demonstrate the functionality of this potentially revolutionary new pharmacokinetic tool. To that end, the PI proposes the following specific aims: 1) Expansion of high precision in vitro use of E-AB sensors to novel drug targets; 2) Expansion of E-AB sensors to measurements in the brain. Successful completion of these aims will not only establish this novel technology and methodology in the PI's laboratory, but will also further develop the technology to measure new, clinically-relevant compounds in a new and important location. Additionally, this work will help develop the PI as an independent research investigator to seek non-SCORE support in the future to expand his research program.
The potential for drug use to develop into an addiction is directly related to the pharmacokinetics of that drug within the brain. Improper dosing of therapeutic compounds based on imprecise pharmacokinetics have contributed to the current opioid epidemic. This project will implement a novel biosensor technology for real-time monitoring of several addictive compounds to evaluate how the body interacts with drugs that cross the blood brain barrier. This new platform usage will inform how drug pharmacokinetics directly in the brain are involved in substance abuse and addiction.