Silver Nanoparticle-Doped Poly(8-Anilino-1-Naphthalene Sulphonic Acid)/CYP2E1 Nanobiosensor for Isoniazid - A First Line Anti-Tuberculosis Drug

Abstract

The Directly Observed Treatment, Short-course (DOTS) constitutes the main strategy for the control of tuberculosis (TB). However, isoniazid (INZ) one of the drugs used in the regimen is potentially hepatotoxic and may lead to drug-associated hepatitis. During TB treatment, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring of INZ to prevent hepatic dysfunction for those patients at risk of drug-induced hepatotoxicity. Proposed herein is a sensitive and simple electrochemical method for the determination of INZ where the proposed PANSA/PVP-AgNPs/CYP2E1 modified Au electrode provides strong electrocatalytic activity toward INZ. High Resolution Transmission Microscopy (HR-TEM) and Electrochemical Impedance Spectroscopy (EIS) studies of PANSA/PVP-AgNPs/CYP2E1 revealed that the nanocomposite PANSA/PVP-AgNPs is highly electroactive and biocompatible with a morphology ideal for the immobilization of CYP2E1. With the advantages of a wide linearity (2 µM – 22 µM) which covers the peak INZ serum level value of 3 µg/mL (22 µM), a good sensitivity of 1.25 µA/ µM and a low detection limit of 0.65 µM, this proposed nanobiosensor holds great potential for the determination of INZ in human samples. The practicality of the nanobiosensor has been successfully demonstrated through the determination of INZ in commercially available pharmaceutical tablets using steady state amperometry, CV and DPV. Michaelis-Menten parameters such as KM, KMapp and IMAX were calculated to be 1.9 x 10-6 A, 1.34 µM and 5.8 µM respectively thus confirming the suitability of the proposed nanobiosenors for use in human samples.