Abstract
The pharmaceutical industry is facing enormous challenges due to high drug attribution rates. For the past decades, novel methods have been developed for safety and efficacy testing, as well as for improving early development stages. In vitro screening methods for drug-receptor binding are considered to be good alternatives for decreasing costs in the identification of drug candidates. However, these methods require lengthy and troublesome labeling steps. Biosensors hold great promise due to the fact that label-free detection schemes can be designed in an easy and low-cost manner. In this paper, for the first time in the literature, we aimed to compare the potential of label-free optical and impedimetric electrochemical biosensors for the screening of antipsychotic drugs (APDs) based on their binding properties to dopamine receptors. Particularly, we have chosen a currently-used atypical antipsychotic drug (Buspirone) for investigating its dopamine D3 receptor (D3R) binding properties using an impedimetric biosensor and a nanoplasmonic biosensor. Both biosensors have been specifically functionalized and characterized for achieving a highly-sensitive and reliable analysis of drug-D3R binding. Our biosensor strategies allow for comparing different affinities against the D3R, which facilitates the identification of strong or weak dopamine antagonists via in vitro assays. This work demonstrates the unique potential of label-free biosensors for the implementation of cost-efficient and simpler analytical tools for the screening of antipsychotic drugs.
Highlights
Drug development is a very complex and lengthy process with an estimated 13 years from laboratory to market, including four years of preclinical research and nine years in the clinical development phase [1]
For the first time, we have investigated the potential of two label-free platforms for receptor-based antipsychotic drugs (APDs) screening: an electrochemical biosensor based on electrochemical impedance spectroscopy (EIS), and a nanoplasmonic sensor based on spectroscopic imaging
We use D3 receptor (D3R) as the receptor and either DA or buspirone as ligands to be able to detect the changes on electrode surface via Nyquist plots represented by Figure 1C
Summary
Drug development is a very complex and lengthy process with an estimated 13 years from laboratory to market, including four years of preclinical research and nine years in the clinical development phase [1]. The preclinical evaluation of drug efficacy is a very costly step and one of the most challenging in early drug development [9]. In this phase, the in vitro screening and analysis of drug interactions with the cellular receptors is essential to determine the mechanism of action, i.e., which receptor it binds, and to quantify the affinity and obtain preliminary dose-response curves [10]. It is necessary to establish analytical methods that enable accurate drug-receptor binding analysis, as well as the efficient screening of several drug candidates, reducing time and costs in the development process
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
