Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents

Michal T. Krauze, Ryuta Saito, Charles Noble, Matyas Tamas, John Bringas, John W. Park, Mitchel S. Berger, Krystof Bankiewicz

Research output: Contribution to journalArticlepeer-review

164 Citations (Scopus)

Abstract

Object. Clinical application of the convection-enhanced delivery (CED) technique is currently limited by low infusion speed and reflux of the delivered agent. The authors developed and evaluated a new step-design cannula to overcome present limitations and to introduce a rapid, reflux-free CED method for future clinical trials. Methods. The CED of 0.4% trypan blue dye was performed in agarose gel to test cannula needles for distribution and reflux. Infusion rates ranging from 0.5 to 50 ml/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macaca fascicularis) by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Results of agarose gel studies showed reflux-free infusion with high flow rates using the step-design cannula. Data from the study in rats confirmed the agarose gel findings and also revealed increasing tissue damage at a flow rate above 5-μl/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. Conclusions. The authors developed a new step-design cannula for CED that effectively prevents reflux in vivo and maximizes the distribution of agents delivered in the brain. Data in the present study show reflux-free infusion with a constant volume of distribution in the rat brain over a broad range of flow rates. Reflux-free delivery of liposomes into nonhuman primate brain was also established using the cannula. This step-design cannula may allow reflux-free distribution and shorten the duration of infusion in future clinical applications of CED in humans.

Original languageEnglish
Pages (from-to)923-929
Number of pages7
JournalJournal of neurosurgery
Volume103
Issue number5
DOIs
Publication statusPublished - 2005 Nov

Keywords

  • Central nervous system
  • Convection-enhanced delivery
  • Liposome
  • Macaca fascicularis
  • Rat
  • Reflux
  • Step-design cannula

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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