european journal of pharmaceutical sciences 30 ( 2 0 0 7 ) 7–14 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/ejps Irinotecan drug eluting beads for use in chemoembolization: In vitro and in vivo evaluation of drug release properties Rachel R. Taylor, Yiqing Tang, M. Victoria Gonzalez, Peter W. Stratford, Andrew L. Lewis ∗ Biocompatibles UK Ltd., Farnham Business Park, Weydon Lane, Farnham, Surrey GU9 8QL, UK article info Article history: Received 8 May 2006 Accepted 5 September 2006 Published on line 15 September 2006 Keywords: Irinotecan drug eluting beads Chemoembolization Drug release In vitro:in vivo correlation abstract Drug eluting beads that release irinotecan in a controlled manner may be useful for appli- cation in the chemoembolization of colorectal cancer metastases to the liver. In this study, irinotecan drug eluting beads were prepared with loadings up to 50mg 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 × 10 -9 and 1.4 × 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 ∼27 kPa to a maximum of about 49 kPa), with increasing drug loading. This did not how- ever, 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 emboliza- tion procedure. The in vivo data were shown to correlate well with the in vitro release measured using a T-apparatus model of embolization. © 2006 Elsevier B.V. All rights reserved. 1. Introduction Despite the existence of excellent screening and preventive strategies, colorectal carcinoma remains a major public health problem in western countries. The American Cancer Society estimates there will be 145,290 new cases diagnosed in 2005, and 56,290 people will die of the disease. In the UK, about 36,000 new cases were diagnosed in 2002, and 17,190 people died of colorectal cancer (Ferlay et al., 2004). Colorectal carci- noma is the third leading cause of death from cancer in both males and females in the USA. It is also the third most com- mon malignancy in both men (after prostate and lung cancers) and women (after breast and lung cancers). ∗ Corresponding author. Tel.: +44 1252 732819. E-mail address: andrew.lewis@biocompatibles.com (A.L. Lewis). Five-year survival rates have improved in recent years for patients with stages I–III colorectal carcinomas; for patients with early, localized disease the survival rate is 90%. Survival has improved through the use of adjuvant chemotherapy for colon cancer and adjuvant chemoradiation for rectal cancer. By the time they are diagnosed, some 25% of colon cancers will have extended through the bowel wall, whereas cancers of the rectum will have spread through the bowel wall in 50–70% of patients and metastasized to lymph nodes in 50–60%. The most common site of extralymphatic involvement is the liver, with the lungs the most frequently affected extra-abdominal organ. Patients with metastatic colorectal tumours frequently die of hepatic failure due to liver metastases. 0928-0987/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ejps.2006.09.002