Gold nanoparticles based sensor for in vitro analysis of drug-drug interactions using imipramine and isoniazid drugs: A proof of concept approach

Prediction of drug-drug interactions (DDIs) before their manifestation is of paramount importance in the development of drug-dosing protocols and drug-design. In this context, we proposed for the first time, gold nanopaticles (AuNPs) based sensor for in vitro assessment of DDIs. Here, we first conducted in-situ molecular docking and simulations studies to interrogate DDIs that allowed predictions of DDIs between two model drugs, such as imipramine (antidepressant) and isoniazid (anti-tuberculosis). This was followed by in vitro studies involving imipramine conjugated gold nanoparticles (Imipramine-AuNPs) as probes for screening DDIs. Association of isoniazid with imipramine molecules over the surface of AuNPs sensor occurred that was confirmed by a combination of physico-chemical methods. Electrochemical investigations revealed the quantitative association of imipramine and isoniazid molecules, where a linear relationship of peak current (Ip) was observed for increasing concentrations of isoniazid from 31 to 667 μM at Imipramine-AuNPs modified Screen Printed Electrodes (SPE), validating the predicted DDIs. The current study aims to highlight the possible interaction between the two drugs that provides valuable information useful for the prediction of similar types of DDIs with other drug pairs.