Multi-panel drugs detection in human serum for personalized therapy.

Area of Science:

• Electrochemistry
• Biotechnology
• Nanomaterials

Background:

• Cytochrome P450 enzymes (CYPs) are crucial for drug metabolism.
• Developing sensitive and selective biosensors for drug monitoring is essential for personalized medicine.
• Multiwalled carbon nanotubes (MWCNT) offer unique electrochemical properties for biosensor development.

Purpose of the Study:

• To develop and characterize P450 biosensors utilizing MWCNT for enhanced drug detection.
• To investigate the impact of MWCNT on the sensitivity and detection limits of CYP isoforms (3A4, 2B4, 2C9).
• To propose a mathematical model for discriminating drug contributions in mixtures and explore applications in personalized therapy.

Main Methods:

• Fabrication of P450 biosensors incorporating MWCNT with specific cytochrome isoforms (CYP3A4, CYP2B4, CYP2C9).
• Electrochemical characterization of biosensor performance, including sensitivity and limit of detection (LOD) for various drug substrates.
• Development and application of a novel mathematical model for analyzing competitive kinetics and drug ratios in mixtures.

Main Results:

• MWCNT integration significantly enhanced biosensor sensitivity for Benzphetamine (CYP2B4), Cyclophosphamide (CYP3A4), and Naproxen (CYP2C9).
• The limit of detection for Cyclophosphamide and Naproxen was substantially decreased using MWCNT, enabling detection within the pharmacological range in human serum.
• The proposed mathematical model successfully discriminated drug contributions in binary mixtures based on electrochemical data and competitive kinetics.

Conclusions:

• MWCNT-based P450 biosensors provide superior performance for drug detection compared to conventional methods.
• The developed biosensors and analytical model facilitate accurate drug quantification and mixture analysis.
• This approach holds significant potential for advancing personalized therapy through real-time drug monitoring.