The mechanisms of drug transport within the body play a critical role in targeted drug delivery and, thus, in the successful treatment of disease. Our research program aims to understand exactly how such mechanisms work by monitoring, in real time, drug levels (and drug disposition dynamics) in vivo. The results of our work could shed light into, for example, the design of drugs with improved, tissue-specific permeability or into the development of strategies to eliminate transport-dependent drug resistance and toxicity. To accomplish our goals, we pursue three major research tracks:
We rely on biomolecular receptors to achieve specificity in our measurements. We select these via modified systematic evolution of ligands by exponential enrichment (SELEX) approaches, developed either within our group or in the laboratories of partners and collaborators. As a first approach, we are building a library of DNA-based biosensors to develop our ability to track many pharmacological agents in vivo. We are not interested in DNA only, however, and are seeking to develop receptors with other natural and non-natural chemistries. A significant part of our efforts involve the engineering of receptors to support efficient signal transduction to electronic interfaces.
Our ability to detect molecular targets in vivo strongly depends on the characteristics of implantable electronic devices. We focus a part of our efforts on designing and fabricating electronic platforms that tolerate prolonged exposure to biological fluids, are minimally invasive, and enable high signal-to-noise measurements. Moreover, we devote significant efforts to the development of software for the real-time control and processing of electrochemical measurements. Check out some of our publications related to this research track:
- Open Source Software for the Real-Time Control, Processing, and Visualization of High-Volume Electrochemical Data. Curtis, S.D.; Ploense, K.L.; Kurnik, M.; Ortega, G.; Parolo, C.; Kippin, T.E.; Plaxco, K.W.; Arroyo-Currás, N.; Anal. Chem., 2019, DOI: 10.1021/acs.analchem.9b02553
Our ultimate goal is to solve important problems in pharmacology. For example, we measure drug transport within the body to characterize any mechanisms involved in the development of drug resistance or toxicity. We are also interested in achieving metabolism-responsive dosing by investigating different types of feedback controllers that can be supported by our continuous measurements.