UC Santa Barbara

Personalized medicine, a rapidly evolving field of healthcare, aims to improve therapeuticoutcomes by individualizing patient care. Therapeutic drug monitoring (TDM) presents a vast improvement to personalized medicine, enabling clinicians to optimize dosing regimens to improve therapeutic outcomes while minimizing toxicity. The state of the art of TDM is significantly limited by the current techniques employed to perform it. Existing technologies are limited by reliance on ex vivo quantification that generally results in single time point or low temporal resolution measurements and the inability to measure drug levels in different physiological compartments simultaneously. Electrochemical aptamer-based (EAB) sensors, a novel biosensing platform, present a powerful means of overcoming these limitations, providing seconds-resolved, cross-compartment measurements of drug distribution in real time. Centered around the focus of advancing TDM, this work first utilizes EAB sensors to better elucidate drug transport from blood to solid tissue, with the ultimate goal of improving transport into the brain. Using doxorubicin as a testbed, I first demonstrate that EAB sensors can capture the distribution of chemotherapeutics from the bloodstream to the peripheral subcutaneous tissue. I then utilize these measurements to perform high-precision feedback-controlled drug delivery over plasma drug levels. After careful evaluation of the permeation of drugs into tissue not separated by a physiological barrier, I then demonstrate the in-brain EAB platform can explore how pharmacological manipulations and drug encapsulation methods may improve drug permeation into the brain. Finally, this work utilizes individual, subject-specific measurements to suggest EAB sensors could be used to inform inter-patient pharmacokinetic variability. Collectively, this work argues that EAB sensors could significantly advance both our understanding of drug transport to the brain and peripheral tissues and revolutionize personalized medicine by enabling high-precision therapeutic drug monitoring.