Physiological Transport Forces Govern Drug Distribution for Stent-Based Delivery

• DOI: 10.1161/hc3101.092214
• Publication Date: 2007-09-28T18:31:09Z
• Authors: Chao-Wei Hwang; David Wu; Elazer R. Edelman
• Keywords: Péclet number

Background The first compounds considered for stent-based delivery, such as heparin, were chosen on the basis of promising tissue culture and animal experiments, yet they have failed to stop restenosis clinically. More recent compounds, paclitaxel, are a different sort, being hydrophobic in nature, their effects after local release seem far more profound. This dichotomy raises question whether drugs that an effect when released from stent do so because differences biology or physicochemical properties targeting. Methods Results We applied continuum pharmacokinetics examine transport forces device geometry distribution stent-delivered hydrophilic drugs. found delivery invariably leads large concentration gradients, with drug concentrations ranging nil several times mean over few micrometers. Concentration variations function Peclet number (Pe), ratio convective diffusive forces. Although exhibited greater variability than drugs, achieved higher remained closer intima. Inhomogeneous strut placement influenced negatively dramatically affecting without changing concentrations. Conclusions Because gradients inextricably linked biological effect, our results provide potential explanation variable success delivery. conclude mere proximity devices tissues does not ensure adequate targeting, physiological cause deviate significantly