Microneedle-Based Continuous Levodopa Monitoring in Patients with Parkinson's Disease.

Optimal levodopa (L-Dopa) dosing for the personal management of Parkinson's disease represents a major clinical challenge due to L-Dopa's narrow therapeutic window and inter- and intra-patient absorption variability. Current methods for measuring L-Dopa, relying on repeated blood draws for centralized laboratory measurements, fall short of capturing dynamic L-Dopa fluctuations that are relevant for timely interventions. Here, we present a minimally invasive microneedle (MN)-based wearable biosensor for continuous monitoring of L-Dopa (CDM) in human subjects. The MN biosensor platform relies on a tyrosinase-functionalized working electrode for detecting L-Dopa in interstitial fluid (ISF) through enzymatic electrochemical detection. The device was evaluated in healthy volunteers and participants with Parkinson's disease in clinical settings, illustrating its ability to provide actionable temporal insights. Critical validation of the MN biosensor was carried out by comparing the ISF L-Dopa signals with plasma L-Dopa concentrations measured by high-performance liquid chromatography (HPLC). Using subject-specific calibration and lag-time correction, the ISF-derived drug profiles showed a close correlation with plasma L-Dopa pharmacokinetics, with a mean absolute relative difference (MARD) of 9.64%. An inverse correlation between the L-Dopa pharmacokinetics and the corresponding motor performance was observed. Such pioneering demonstration of the clinical feasibility of MN-based CDM in humans highlights its considerable potential for supporting the management of Parkinson's disease.