In recent years, targeted drug delivery systems have been regarded as a promisingsolution to enhance the efficiency of treatments against clots in blood vessels. Inthis context, shear-activated nanotherapeutics (SANTs) have been recently proposed.These are micrometric clusters of polymeric nanoparticles coated with a clotlysingagent. These drug carriers are stable under normal blood flow conditions, but theycan be designed to undergo breakup right on the clot in response to the local increasein the hydrodynamic stress caused by the lumen restriction, effectively concentrat-ing the active agent at the point of need. The aim of this work is to investigate themechanical response of three potential drug carrier morphologies to the pathologicalflow field stress, typically encountered in obstructed blood vessels. Computationalfluid dynamics simulations have been used to compare the viscous stress in arterialobstructions with the one in a microfluidic device, suitable for in-vitro experimen-tal tests. Discrete element method simulations built upon Stokesian dynamics wereconducted to estimate the tensile stress distribution acting inside isostatic, randomclose packing, and hollow aggregates. The results herein presented constitute a plat-form for a future experimental campaign and aim at establishing SANTs as a robustand broadly applicable targeting strategy.

Response of shear‐activated nanotherapeutic particles in a clot‐obstructed blood vessel by CFD‐DEM simulations

Arima, Valentina;Baldassarre, Francesca;
2022

Abstract

In recent years, targeted drug delivery systems have been regarded as a promisingsolution to enhance the efficiency of treatments against clots in blood vessels. Inthis context, shear-activated nanotherapeutics (SANTs) have been recently proposed.These are micrometric clusters of polymeric nanoparticles coated with a clotlysingagent. These drug carriers are stable under normal blood flow conditions, but theycan be designed to undergo breakup right on the clot in response to the local increasein the hydrodynamic stress caused by the lumen restriction, effectively concentrat-ing the active agent at the point of need. The aim of this work is to investigate themechanical response of three potential drug carrier morphologies to the pathologicalflow field stress, typically encountered in obstructed blood vessels. Computationalfluid dynamics simulations have been used to compare the viscous stress in arterialobstructions with the one in a microfluidic device, suitable for in-vitro experimen-tal tests. Discrete element method simulations built upon Stokesian dynamics wereconducted to estimate the tensile stress distribution acting inside isostatic, randomclose packing, and hollow aggregates. The results herein presented constitute a plat-form for a future experimental campaign and aim at establishing SANTs as a robustand broadly applicable targeting strategy.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11587/470509
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