Feedback Control over Plasma Drug Concentrations Achieves Rapid and Accurate Control over Solid-Tissue Drug...

Area of Science:

• Biomedical Engineering
• Pharmacology
• Sensor Technology

Background:

• Electrochemical aptamer-based (EAB) sensors allow continuous, real-time monitoring of drugs and biomarkers in various tissues of live subjects.
• Real-time data from EAB sensors facilitate closed-loop, feedback-controlled drug delivery systems.
• The efficacy of many drugs relies on their concentration at the site of action within solid tissues, not just in plasma.

Purpose of the Study:

• To experimentally confirm that stable plasma drug concentrations result in stable interstitial fluid (ISF) drug concentrations.
• To demonstrate the use of EAB sensors for feedback control of chemotherapeutic drug concentrations in vivo.
• To validate the precision and reliability of EAB sensors for real-time monitoring in biological tissues.

Main Methods:

• Utilized an intravenous EAB sensor to control doxorubicin concentration in live rat plasma.
• Employed a second EAB sensor in the subcutaneous space to monitor ISF drug concentrations.
• Used paired EAB sensors in the ISF to assess sensor-to-sensor tracking and precision.

Main Results:

• Maintaining controlled plasma drug concentrations led to matching and stable drug concentrations in the ISF within 30-60 minutes.
• ISF drug concentrations accurately tracked plasma concentrations with a root-mean-square deviation of 8% to 21%.
• Paired ISF sensors demonstrated high precision, with R-squared values ranging from 0.95 to 0.99.

Conclusions:

• Feedback-controlled plasma drug concentrations effectively regulate drug levels in solid tissues, validating EAB sensor use for controlling drug action sites.
• In vivo EAB sensor performance closely matches in vitro validation studies, indicating high reliability.
• EAB sensors offer a promising approach for precise, personalized drug dosing and therapeutic monitoring.