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European Biopharmaceutical Review

Microphysiological Systems Emerging as Powerful Tools for Drug Discovery

Given that only one in ten preclinical candidates in Phase I trials are likely to gain market approval, better predictors of clinical success are urgently needed (1). Translating findings from in vitro studies to in vivo settings remains a challenge because of species differences in pharmacokinetics and pharmacodynamics (PKPD), oversimplified in vitro models, and an insufficient understanding of the underlying pathophysiology. Termination is often attributed to safety issues identified in animal studies, which could be minimised with more accurate predictions of absorption, distribution, metabolism, and excretion (ADME) profiles (2).

While 2D monolayer cell culture experiments and animal models are deeply embedded in the pharmaceutical infrastructure, clear gaps, inefficiencies, and inaccuracies exist, creating a need for new alternative and complementary research models (3). At the cross-section of bioengineering and cell biology lies a new approach to drug discovery and development, which is being pursued to help overcome the notoriously low clinical success rate. Microphysiological systems (MPS) are an emerging class of in vitro models expected to expedite drug discovery by providing robust physiologically relevant data at critical stages of R&D (4).

Micro-Engineering Meets Physiology

MPS encompass a range of platforms that mimic aspects of organ function by using microengineering technology, often combined with 3D microenvironments (5). Such systems have been reported as 3D spheroids, organoids, organon- a-chip, multi-organs on chips, static micropatterned technologies, and physiome-on-a-chip models (5-6). In these platforms, living cells and microfluidic technologies are combined with some form of drug delivery, stimulation, and/ or sensing tools. Organ-on-a-chip (OOC) models can exist as single systems or as connected units that simulate elements of organ crosstalk. MPS build on concepts harnessed by traditional two-dimensional assays and include design features that improve physiological relevance, such as (2):

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Dr Audrey Dubourg is CN Bio’s Product Manager for their PhysioMimix™ Organ-On-Chip lab benchtop platform, which enables researchers to model human biology in the lab through rapid and predictive 3D tissue-based studies harnessing microfluidic technology. Audrey has an extensive research background in microbiology and parasitology, with significant experience in molecular biology techniques and 3D mammalian cell culture employing MPS technologies. Audrey gained her PhD at the University of East Anglia, UK and carried out a postdoctoral scholarship at the University of California, US.
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Dr Audrey Dubourg
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