Cytochrome P450 2E1/Nickel-Poly(propylene imine) dendrimeric nanobiosensor for pyrazinamide - A first line TB Drug

Abstract

The tuberculosis (TB) disease to this day remains one of the world’s prominent killerdiseases. Pyrazinamide (PZA) is one of the most commonly prescribed anti- tuberculosis (anti-TB) drugs due to its ability to significantly shorten the TB treatment period from the former nine months to the current six months duration. However, excess PZA in the body causes hepatotoxicity and damages the liver. This hepatotoxicity, together with the resistance of the bacteria to treatment drugs, poor medication and inappropriate dosing, greatly contribute to the high incidents of TB deaths and diseases that are due to side effects (such as liver damage). This brings about the calls for alternative methods for ensuring reliable dosing of the drug, which will be specific from person to person due to inter-individual differences in drug metabolism. A novel biosensor system for monitoring the metabolism of PZA was prepared with a Ni-PPI-PPy star copolymer and cytochrome P450 2E1 (CYP2E1) deposited onto a platinum electrode. The nanobiosensor system exhibited enhanced electro-activity that is attributed to the catalytic effect of the incorporated star copolymer. The biosensor had a sensitivity of 0.142 µA.nM-1, and a dynamic linear range (DLR) of 0.01 nM-0.12 nM (1.231 – 7.386 ng/L PZA). The limit of detection of the biosensor was found to be 0.00114 nM (0.14 ng/L) PZA. From the HPLC peakconcentration (Cmax) of PZA determined 2 h after drug intake is 2.79 – 3.22 ng.L-1,which is very detectable with the nanobiosensor as it falls within the dynamic linear range.