Doxorubicin and mitoxantrone drug eluting beads for the treatment of experimental peritoneal carcinomatosis in colorectal cancer†
Michael Keese
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
The first two authors contributed equally to this work.
Search for more papers by this authorLala Gasimova
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
The first two authors contributed equally to this work.
Search for more papers by this authorKay Schwenke
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorVugar Yagublu
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorEdward Shang
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorRalf Faissner
Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorAndrew Lewis
Biocompatibles UK Ltd, Weydon Lane, Farnham, Surrey, United Kingdom
Search for more papers by this authorCorresponding Author
Matthias Löhr
Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Department of Surgical Gastroenterology, Karolinska University, Stockholm, Sweden
Fax: +46-85-858-2340
Department of Surgical Gastroenterology, Karolinska University, Stockholm, SwedenSearch for more papers by this authorMichael Keese
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
The first two authors contributed equally to this work.
Search for more papers by this authorLala Gasimova
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
The first two authors contributed equally to this work.
Search for more papers by this authorKay Schwenke
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorVugar Yagublu
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorEdward Shang
Department of Surgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorRalf Faissner
Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Search for more papers by this authorAndrew Lewis
Biocompatibles UK Ltd, Weydon Lane, Farnham, Surrey, United Kingdom
Search for more papers by this authorCorresponding Author
Matthias Löhr
Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
Department of Surgical Gastroenterology, Karolinska University, Stockholm, Sweden
Fax: +46-85-858-2340
Department of Surgical Gastroenterology, Karolinska University, Stockholm, SwedenSearch for more papers by this authorStatement: A.L. is director of the company that sponsored the study and provided the materials. No restrictions were placed upon publication of any results.
Abstract
We investigated the therapeutic efficiency of sulfonate-modified polyvinyl alcohol beads loaded with doxorubicin, irinotecan or mitoxantrone in vitro and in vivo in a model of experimental peritoneal carcinomatosis (PC). In vitro, cell proliferation was efficiently impaired by doxorubicin drug eluting bead (DEB) treatment while mitoxantrone DEBs were less effective than. Irinotecan showed little effect for both DEBs and free drug. Apoptosis was not different between free mitoxantrone and the DEB form while more apoptosis induction was observed in cells incubated with free doxorubicin and irinotecan. Experimental PC was produced in mice. The therapeutic efficiency of either mitoxantrone and doxorubicin DEB or free drugs were compared. Mice were treated either once on day 12 or by 3 repetitive applications on days 7, 10 and 12. Mice treated by DEBs showed less weight loss and mortality. Therapeutic effect was determined by measuring tumor volume and tumor load on the day 15 after tumor inoculation. For the single application on the day 12, an advantage could be observed for the free drugs. After 3 repeated injections of both free and mitoxantrone DEB no difference in tumor load or tumor volume could be observed. Least tumor load and tumor volume was observed in mice that received 3 repeated injections of doxorubicin DEB. No animal survived 3 injections of free doxorubicin. We conclude that bead encapsulation of chemotherapeutic drugs may show the advantage of less toxicity in peritoneal spread of colorectal cancer. © 2008 Wiley-Liss, Inc.
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