Resilient nanostructured bioanalytic microneedle longitudinally monitors preclinical renal and hepatic drug clearance and dysfunction

Key findings from this study

• The researchers demonstrate that resilient nanostructured bioelectrodes maintain functional stability for 6 days in vivo while resisting mechanical damage from tissue abrasion.
• The study found that interstitial fluid drug clearance measurements accurately represent blood pharmacokinetic parameters through equilibrium-based bioanalytical analysis.
• The authors report that the platform detected hepatic clearance impairment in liver-damaged models and renal dysfunction earlier than conventional biomarker thresholds through quantified drug clearance.

Overview

Resilient nanostructured bioelectrodes integrated into microneedles enable continuous monitoring of drug clearance and organ dysfunction through wearable electrochemical biosensing. The platform addresses fundamental limitations of existing wearable biosensors: sensitivity constraints and mechanical failure from tissue abrasion. Bilayer electrode architecture combines gold adhesion layers with controlled dealloying to produce corrosion-resistant, high signal-to-noise ratio biosensors stable across wide electrochemical potential windows.

Methods and approach

Researchers fabricated resilient nanostructured bioelectrodes using a bilayer process that strengthens electrodes with micrometer-thick gold adhesion layers and reduces stress through controlled dealloying. The resulting nanocavity-textured interfaces integrate receptor-based electrochemical biosensors. In vivo validation occurred in freely moving rats over 6-day monitoring periods. Pharmacokinetic analysis employed a blood-interstitial fluid equilibrium-based bioanalytical framework to derive blood-equivalent parameters from interstitial fluid measurements. Hepatic clearance assessment utilized irinotecan in liver-damaged animal models. Renal function evaluation compared drug clearance measurements across chronic kidney disease severity grades.

Results

The resilient nanostructured bioelectrodes maintained functional stability for 6 days in vivo while remaining resistant to tissue abrasion despite mechanical stress from megapascal-stiff tissue environments. Artifact-free measurements with enhanced active surface area and antifouling properties enabled quantification of pharmacokinetic parameters equivalent to blood concentrations. In hepatic studies, the platform detected delayed irinotecan clearance in liver-damaged models compared to controls. Renal function monitoring revealed drug clearance measurements that correlated with blood antibiotic pharmacokinetics across varying chronic kidney disease severities and detected renal impairment earlier than conventional biomarker thresholds through clearance quantification.

Implications

Longitudinal interstitial fluid monitoring of drug clearance provides a minimally invasive pathway for real-time organ function assessment without repeated blood sampling. The platform enables precision dosing for narrow therapeutic index drugs by continuously tracking pharmacokinetic parameters in individual subjects. Early detection of hepatic and renal dysfunction through quantified drug clearance creates clinical opportunities for therapeutic intervention before biomarker thresholds are exceeded. Integration of electrochemical biosensors into durable microneedle architectures extends feasibility of wearable bioanalytic systems for clinical pharmacokinetics monitoring and personalized medicine applications.

Scope and limitations

This summary is based on the study abstract and available metadata. It does not include a full analysis of the complete paper, supplementary materials, or underlying datasets unless explicitly stated. Findings should be interpreted in the context of the original publication.