A nanoMIP sensor for real-time in vivo monitoring of levodopa pharmacokinetics in precision Parkinson's therapy.

Abstract

Real-time in vivo monitoring of levodopa pharmacokinetics is essential to address its narrow therapeutic window in Parkinson's disease (PD) therapy. However, current methods require excessive sample volumes, suffer low sampling frequencies, and fail to capture complete pharmacokinetic profiles. Here, we present an in vivo monitoring system for real-time tracking of levodopa levels in interstitial fluid (ISF) using a spindle-shaped carbon nanotube (CNT) fiber electrochemical sensor functionalized with a nanoscale molecularly imprinted polymer (nanoMIP) on single electroactive CNTs. The core-shell (CNT-nanoMIP) nanostructures provide sensitive, selective detection of levodopa, along with resistance to both biofouling and chemical fouling in continuous ISF detection. The system was validated for monitoring complete pharmacokinetic profiles and assessing temporal correlations between ISF/plasma levodopa pharmacokinetics in both PD rat models and healthy rats. We also demonstrated optimized and adjustable pharmacokinetic profiles through in vivo experiments with rationally designed levodopa dosing regimens, highlighting the system's potential for personalized PD pharmacotherapy.