Abstract
Mechanopharmacology is an emerging interdisciplinary field that
investigates drug action using biomechanically appropriate in vitro
systems to the relevant (patho)physiology. This review outlines emerging
technologies and techniques which aim to bridge the gap between
mechanical cues influencing cellular biology and conventional
pharmacology. We delve into the impact of mechanopharmacology on drug
development in cancers and fibrotic diseases. Mechanical cues such as
stretch, stiffness, circadian rhythms, fluid flow, intercellular
signalling cascades and cytoskeletal structures can modulate drug
interactions with molecular targets with implications for drug discovery
and development. Models incorporating mechanopharmacological cues to
investigate pharmacokinetics, pharmacodynamics and therapeutic outcomes
are outlined. Furthermore, this review discusses innovations in the use
of biomaterials and microfluidics, to enable further the emulation of
the mechanical microenvironment. We advocate for the application of
mechanopharmacological considerations to improve the physiological
relevance of methods used in the drug discovery pipeline.