We have demonstrated the first ever example of closed-loop feedback control over plasma drug levels informed by real-time in-vivo drug measurements. We achieved this using a sensing architecture that is independent of the chemical reactivity of the target molecule, rendering the approach, at least in theory, generalizable to any drug. Here we propose a research and development program aimed at translating this innovative breakthrough into a powerful new tool applicable to both pharmacological research and clinical practice. By improving (by orders of magnitude) the precision with which we can control in-vivo drug levels, the proposed technology would render pharmacokinetics an experimentally controllable parameter, allowing researchers to more precisely map the relationships between pharmacokinetics and clinical outcomes, to eliminate pharmacokinetic inconsistency as a confounding experimental variable, and to accurately simulate human pharmacokinetics in animal models. Ultimately, such a technology could be used in the clinic where, by optimize dosing moment-to-moment in response to a patient's changing metabolism, it would ensure that a therapy's benefits are maximized while its risks are minimized.

Public Health Relevance

By providing, for the first time ever, a means of actively and precisely controlling the level of a drug in the living body, the availability of closed-loop feedback-controlled drug delivery could significantly impact both medical research and clinical practice. Such an advance would, for example, enable access to unprecedentedly reproducible pharmacokinetics in research, the accurate simulation of human pharmacokinetics in animal models, and, ultimately, the safer, more effective delivery of drugs to human patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI145206-01
Application #
9761770
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Shabman, Reed Solomon
Project Start
2019-01-14
Project End
2022-12-31
Budget Start
2019-01-14
Budget End
2019-12-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Santa Barbara
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106