Irinotecan drug eluting beads for use in chemoembolization: In vitro and in vivo evaluation of drug release properties

Drug eluting beads that release irinotecan in a controlled manner may be useful for application in the chemoembolization of colorectal cancer metastases to the liver. In this study, irinotecan drug eluting beads were prepared with loadings up to 50 mg drug/mL hydrated beads. Drug loading was via an ion-exchange mechanism with sulfonate binding sites in the bead. Release in vitro was shown to be sustained and dependent upon the presence of ions in the elution medium, drug loading and bead size. Drug elution in PBS was controlled by solute diffusion within the beads and gave rise to values for the diffusion coefficient, D, of between 2.4 x 10(-9) and 1.4 x 10(-7) cm(2) s(-1). The beads were shown to decrease in size (by a maximum 25-30%), and concomitantly their modulus of compression increased (from similar to 27 kPa to a maximum of about 49 kPa), with increasing drug loading. This did not however, influence their ability to be suspended homogeneously in contrast agent or delivered through a microcatheter. Following porcine hepatic artery embolization, maximum plasma levels were 70-75% lower for both irinotecan and SN-38 compared to intraarterial bolus administration, with peak levels observed at 2 and 5 min after completion of the embolization procedure. The in vivo data were shown to correlate well with the in vitro release measured using a T-apparatus model of embolization. (c) 2006 Elsevier B.V All rights reserved.