Improving reliability and reducing costs of cardiotoxicity assessments using laser-induced cell poration on
Giuseppina Iachetta1, Nicolò Colistra1, Giovanni Melle1
1Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.
Abstract:
Drug-induced cardiotoxicity is a major barrier to drug development and a main cause of withdrawal of marketed drugs. Drugs can strongly alter the spontaneous functioning of the heart by interacting with the cardiac membrane ion channels. If these effects only surface during in vivo preclinical tests, clinical trials or worse after commercialization, the societal and economic burden will be significant and seriously hinder the efficient drug development process. Hence, cardiac safety pharmacology requires in vitro electrophysiological screening assays of all drug candidates to predict cardiotoxic effects before clinical trials. In the past 10 years, microelectrode array (MEA) technology began to be considered a valuable approach in pharmaceutical applications. However, an effective tool for high-throughput intracellular measurements, compatible with pharmaceutical standards, is not yet available. Here, we propose laser-induced optoacoustic poration combined with CMOS-MEA technology as a reliable and effective platform to detect cardiotoxicity. This approach enables the acquisition of high-quality action potential recordings from large numbers of cardiomyocytes within the same culture well, providing reliable data using single-well MEA devices and single cardiac syncytia per each drug. Thus, this technology could be applied in drug safety screening platforms reducing times and costs of cardiotoxicity assessments, while simultaneously improving the data reliability.
Insights
A new laser-induced optoacoustic poration method combined with microelectrode array (MEA) technology offers a reliable platform for detecting drug-induced cardiotoxicity. This advance improves drug safety screening by providing high-quality intracellular recordings, reducing costs and time.
Area of Science:
- Cardiovascular Pharmacology
- Biomedical Engineering
- Drug Development
Background:
- Drug-induced cardiotoxicity is a significant challenge in drug development, leading to drug withdrawal and substantial economic burdens.
- Cardiac safety pharmacology necessitates in vitro electrophysiological screening to predict cardiotoxic effects early in the drug development pipeline.
- Current microelectrode array (MEA) technologies lack effective tools for high-throughput intracellular measurements suitable for pharmaceutical standards.
Purpose of the Study:
- To introduce a novel platform combining laser-induced optoacoustic poration with CMOS-MEA technology for reliable cardiotoxicity detection.
- To enable high-throughput intracellular measurements of cardiomyocyte function for drug safety screening.
- To enhance the accuracy and efficiency of cardiotoxicity assessments in preclinical drug development.
Main Methods:
- Development of a combined laser-induced optoacoustic poration and CMOS-MEA system.
- Acquisition of high-quality intracellular action potential recordings from cardiomyocytes.
- Utilizing single-well MEA devices for drug testing on single cardiac syncytia.
Main Results:
- The proposed platform enables reliable and effective detection of drug-induced cardiotoxicity.
- High-quality action potential recordings were obtained from multiple cardiomyocytes within a single well.
- The method demonstrated potential for improving data reliability in drug safety screening.
Conclusions:
- Laser-induced optoacoustic poration coupled with CMOS-MEA technology presents a promising solution for pharmaceutical drug safety screening.
- This technology can significantly reduce the time and cost associated with cardiotoxicity assessments.
- The platform offers enhanced data reliability, aiding in the early identification of potential cardiotoxic drugs.
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