Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Abstract

Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy- and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3h was equal to ~0.2 and ~0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partially-confined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully-confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation.