Abstract:
An improved method for evaluating drug release behaviour of drug-eluting embolization beads (DEBs) was developed utilizing an open-loop flow-through system, in which the beads were packed into an occlusive mass within the system and extracted with a flowing elution medium over time. Glass beads were introduced into the beads mass in order to ensure laminar flow, reduce dead volume and improve reproducibility by compensating for swelling phenomena. The effects of glass bead ratio, elution medium flow rate and ion concentration, DEB size and drug concentration and drug type (doxorubicin and irinotecan) were evaluated using DEB composed of a sulfonate-modified polyvinyl alcohol hydrogel (DC Bead™) as the test article. The rate and amount of drug elution from the packed beads was affected by flow rate, the bead size and initial loading dose. The raw data from the concentration profile analysis provided valuable information to reveal the drug elution behaviour akin to the pharmacokinetic data observed for embolized beads (yielding in vitro Cmax and tmax data) which was complementary to the normal cumulative data obtained. A good correlation with historical reported in vivo data validated the usefulness of the method for predicting in vivo drug elution behaviour.
Keywords
Drug-eluting beads; Embolization; Flow-through elution system; Doxorubicin; Ion-exchange.
Citation: Tanya Swaine, Yiqing Tang, Pedro Garcia, Jasmine John, Laura J. Waters, Andrew L. Lewis Evaluation Of Ion Exchange Processes In Drug-eluting Embolization Beads By Use Of An Improved Flow-through Elution Method http://dx.doi.org/10.1016/j.ejps.2016.08.020
Received: 17 June 2016, Revised: 9 August 2016, Accepted: 9 August 2016, Available online: 12 August 2016
Copyright: © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Conclusions
A flow-through device has been tested to evaluate the elution properties of doxorubicin and irinotecan loaded DC Bead™ under a packed state and in sink conditions. By selecting different parameters, such as bead packing, elution medium flow rate, dose of loading, and bead size, it has been demonstrated that the doxorubicin elution was controlled by a film diffusion step, which was supported by the experimental observation that increasing flow rate led to increased drug elution rate. The rate and amount of drug elution from the packed beads was affected by flow rate, the bead size and initial loading dose. In addition to doxorubicin, measurement of elution of irinotecan was also possible on the device, although it has much weaker interaction with the beads. The data from the concentration profile analysis provided valuable information to reveal the drug elution behaviour akin to the pharmacokinetic data observed for embolized beads and complementary to the normal cumulative data. Thus, the flow-through system is a useful tool to evaluate DEBs both in QC and for in vivo mimicking studies.
Acknowledgements
TS is in receipt of a PhD studentship sponsored by Biocompatibles UK Ltd, a BTG International group company.
