Structural biomechanics modulate intramuscular distribution of locally delivered drugs.

Journal of Biomechanics
Peter I Wu, Elazer R Edelman

Abstract

As local drug delivery continues to emerge as a clinical force, so does understanding of its potentially narrow therapeutic window. Classic molecular transport studies are of value but do not typically account for the local nature of drug transport or the effects of regional dynamic function in target tissues like muscle that may undergo cyclical and variable mechanical motion and loading. We examined the impact of dynamic architecture on intramuscular drug distribution. We designed a tissue mounting technique and mechanical loading system that uniquely enables pharmacokinetics investigations in association with control of muscle biomechanics while preserving physiologic tissue architecture. The system was validated and used to elucidate the influence of architecture and controlled cyclic strain on intramuscular drug distribution. Rat soleus muscles underwent controlled deformations within a drug delivery chamber that preserved in vivo physiology. Penetration of 1mM 20 kDa FITC-dextran at planar surfaces of the soleus axial cross-section increased significantly from 0.52+/-0.09 mm under 80 min of static (0%) strain to 0.81+/-0.09 mm under cyclic (3 Hz, 0-20% peak-to-peak) strain, demonstrating the driving effect of cyclic loadi...Continue Reading

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Citations

Apr 28, 2011·Medical Physics·Kevin M MoermanAart J Nederveen
Feb 4, 2014·Nature Medicine·Frank J HernandezJames O McNamara
Apr 17, 2013·Journal of the Mechanical Behavior of Biomedical Materials·Juliette GindreCiaran K Simms
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