Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts

Pin Yuan Chen, Tomoko Ozawa, Daryl C. Drummond, Ashish Kalra, Jonathan B. Fitzgerald, Dmitri B. Kirpotin, Kuo Chen Wei, Nicholas Butowski, Michael D. Prados, Mitchel S. Berger, John R. Forsayeth, Krystof Bankiewicz, C. David James*

*Corresponding author for this work

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Liposomal drug packaging is well established as an effective means for increasing drug halflife, sustaining drug activity, and increasing drug efficacy, whether administered locally or distally to the site of disease. However, information regarding the relative effectiveness of peripheral (distal) versus local administration of liposomal therapeutics is limited. This issue is of importance with respect to the treatment of central nervous system cancer, for which the blood-brain barrier presents a significant challenge in achieving sufficient drug concentration in tumors to provide treatment benefit for patients. Methods. We compared the anti-tumor activity and efficacy of a nanoliposomal formulation of irinotecan when delivered peripherally by vascular route with intratumoral administration by convection-enhanced delivery (CED) for treating intracranial glioblastoma xenografts in athymic mice. Results. Our results show significantly greater antitumor activity and survival benefit from CED of nanoliposomal irinotecan. In 2 of 3 efficacy experiments, there were animal subjects that experienced apparent cure of tumor from local administration of therapy, as indicated by a lack of detectable intracranial tumor through bioluminescence imaging and histopathologic analysis. Results from investigating the effectiveness of combination therapy with nanoliposomal irinotecan plus radiation revealed that CED administration of irinotecan plus radiation conferred greater survival benefit than did irinotecan or radiation monotherapy and also when compared with radiation plus vascularly administered irinotecan. Conclusions. Our results indicate that liposomal formulation plus direct intratumoral administration of therapeutic are important for maximizing the anti-tumor effects of irinotecan and support clinical trial evaluation of this therapeutic plus route of administration combination.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalNeuro-oncology
Volume15
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Convection-enhanced delivery
  • Glioblastoma
  • Irinotecan
  • Liposome
  • Xenograft

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Chen, P. Y., Ozawa, T., Drummond, D. C., Kalra, A., Fitzgerald, J. B., Kirpotin, D. B., Wei, K. C., Butowski, N., Prados, M. D., Berger, M. S., Forsayeth, J. R., Bankiewicz, K., & James, C. D. (2013). Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts. Neuro-oncology, 15(2), 189-197. https://doi.org/10.1093/neuonc/nos305