New body-on-chip prototype for in vitro pharmacokinetic analysis and next-generation risk assessment of drugs

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Discovery and development of new drugs for human use remains a slow, expensive and inefficient process. A critical point of failure in drug discovery programmes is the preclinical evaluation of drug candidates with only about 30% success rate. Consequently, new methodologies to increase success rate at the preclinical drug development stage are needed. This project aims to develop a new, environmentally sustainable, prototype device to allow for high-throughput in vitro characterisation of drugs pharmacokinetics (PK) coupled with in silico kinetic models to better predict drug performance in vivo. The gold-standard approach to investigate drugs PK involves using Positron Emission Tomography (PET) and microdosing techniques. However, these techniques can be expensive and often require a large number of animals. Importantly, although the use of animals can be useful to assess drug distribution, metabolism and therapeutic effects, species differences versus humans often decrease the translational success rate of a new drug. Therefore, there is a need to design more efficient drug discovery pipelines and to increase confidence on selection of the lead compounds at early stages of the process. To this regard, the recent development of the so called "body-on-chip" in vitro technology holds tremendous promise as a platform to predict drug responses in vivo.Recently, our team has developed a new "body-on-chip" prototype device, which has a number of important properties that position it uniquely in the "body-on-chip" arena, namely: Perfusion through the capillary system and organ compartments capable of mimicking the human circulatory system; Easy to use and versatile organ compartment inserts capable of housing a large number of cells, required for accurate quantification of concentration of drugs in cells by high throughput and mainstream chromatographic methods; Environmentally sustainable re-usable design, requiring only a simple clean protocol between experiments; Reduced cost of manufacturing as well as reduced maintenance costs, as the "body-on-chip" can be re-used and the associated peristaltic pump required to maintain flow through the device is commercially available off the shelf. Our new "body-on-chip" device has the potential to enable predictive PK studies in vitro as well as individual tissue drug exposure analysis and drug-target binding kinetics quantification, which currently cannot be accomplished with available "body-on-chip" devices.