Sensing Platform for Antiviral Drug in Pharmaceuticals and Human Physiology Exploiting Electrocatalytic Properties of Carbon Nanomaterials

Abstract

In recent years, much attention has been focused on the preparation of a variety of nanomaterials with highly controllable size, shape, surface charge and physicochemical characteristics. The alluring properties of nanomaterial exhibit signal amplification due to which they are prodigiously used for the fabrication of a wide range of electrochemical sensors. Single walled carbon nanotubes (SWNTs) displaying quantum dots and wires at very low temperatures enhances the electrode conductivity and facilitates the electron transfer between myriad electroactive species and the underlying electrode. Nafion which is a sulfonated tetrafluorethylene copolymer possessing pronounced antifouling capacity, chemical inertness, strong adsorption ability, thermal stability and biocompatibility renders it to be extensively employed as an electrode modifier. Rapid emergence of viral diseases has posed a consequential threat to all human and veterinary health. Over past two decades these diseases are major cause of death among all infectious diseases worldwide. Acyclovir (ACV) which is a synthetic purine based nucleoside analogue plays a pivotal role in the therapy of viral diseases and possesses the best safety profile of all antivirals licensed so far. ACV is an emerging drug for the clinical treatment against herpes simplex virus, hepatitis B virus, varicella zoster virus and epstein-barr virus. ACV is marketed in the form of ophthalmic ointments, dermal cream, injections, capsules and oral tablets which have been extensively and effectively used for the treatment of herpes virus infections. The drug provides remarkable therapeutic benefit in the therapy of viral diseases like cold sores, keratitis, corneal blindness, encephalitis and virally infected central nervous system. Several adverse outcomes like neurotoxicity, nephrotoxicity, urticaria, phlebophlogosis, diarrhoea, cephalalgia, emesis and swoon are associated with higher intake of ACV and its abuse. Various analytical techniques other than electrochemical have several inconveniences which include lengthy and tedious sample preparation procedures, long analysis time and need of trained technicians. Chromatographic methods suffer from consumption of large volumes of high purity organic solvents and requirement of expensive sophisticated instruments. These methods also suffer from lack of selectivity and sensitivity which makes them unsuitable for routine analysis. A simple and sensitive approach is proposed for the accurate monitoring of antiviral drug ACV utilizing glassy carbon electrode (GCE) fabricated with SWNTs and nafion composite film employing square wave voltammetry for the first time. The developed sensor exhibits effective and sustained electron mediating behavior displaying higher peak currents at lower potential than those obtained at bare GCE. The developed sensor engendered ∼2.5 fold larger electroactive surface area in comparison to bare GCE which substantially accelerated the rate of electron transfer via improved electrical conductivity. At optimal experimental conditions, oxidation current showed a wide linear response for ACV in the concentration range from 10 nM to 30 µM. The proposed sensor exhibited pronounced analytical performance for the determination of ACV with limit of detection corresponding to 1.8 nM and high sensitivity of 15.4 µA µM-1. The modified sensor showcased high recognition selectivity, fair reproducibility and long term stability of signal response in the physiological environment. The developed prototype was successfully implemented to quantify ACV in several commercially available pharmaceuticals. The versatile method described herein was efficaciously applied further in detecting ACV in real human urine sample of patient undergoing pharmacological treatment with ACV. The results explicitly demonstrate the applicability of the developed sensor in quality control, pharmacokinetic studies and clinical analysis.