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Electrochemical Aptamer-Based Sensors for Improved Therapeutic Drug Monitoring and High-Precision, Feedback-Controlled Drug Delivery
journal contribution
posted on 2019-10-15, 18:50 authored by Philippe Dauphin-Ducharme, Kyungae Yang, Netzahualcóyotl Arroyo-Currás, Kyle L. Ploense, Yameng Zhang, Julian Gerson, Martin Kurnik, Tod E. Kippin, Milan N. Stojanovic, Kevin W. PlaxcoThe
electrochemical aptamer-based (E-AB) sensing platform appears
to be a convenient (rapid, single-step, and calibration-free) and
modular approach to measure concentrations of specific molecules (irrespective
of their chemical reactivity) directly in blood and even in situ in
the living body. Given these attributes, the platform may thus provide
significant opportunities to render therapeutic drug monitoring (the
clinical practice in which dosing is adjusted in response to plasma
drug measurements) as frequent and convenient as the measurement of
blood sugar has become for diabetics. The ability to measure arbitrary
molecules in the body in real time could even enable closed-loop feedback
control over plasma drug levels in a manner analogous to the recently
commercialized controlled blood sugar systems. As initial exploration
of this, we describe here the selection of an aptamer against vancomycin,
a narrow therapeutic window antibiotic for which therapeutic monitoring
is a critical part of the standard of care, and its adaptation into
an electrochemical aptamer-based (E-AB) sensor. Using this sensor,
we then demonstrate: (i) rapid (seconds) and convenient (single-step
and calibration-free) measurement of plasma vancomycin in finger-prick-scale
samples of whole blood, (ii) high-precision measurement of subject-specific
vancomycin pharmacokinetics (in a rat animal model), and (iii) high-precision,
closed-loop feedback control over plasma levels of the drug (in a
rat animal model). The ability to not only track (with continuous-glucose-monitor-like
measurement frequency and convenience) but also actively control plasma
drug levels provides an unprecedented route toward improving therapeutic
drug monitoring and, more generally, the personalized, high-precision
delivery of pharmacological interventions.
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electrochemical aptamer-basedsubject-specific vancomycin pharmacokineticscontinuous-glucose-monitor-like measurement frequencyElectrochemical Aptamer-Based SensorsE-ABplasma drug levelsrat animal modeldrug monitoringFeedback-Controlled Drug Deliveryplasma drug measurementsTherapeutic Drug Monitoringcontrol plasma drug levelsclosed-loop feedback controlhigh-precisionblood sugar systems
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