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

• Published in: Journal of neurosurgery Vol. 103; no. 5; p. 923
• Main Authors: Krauze, Michal T, Saito, Ryuta, Noble, Charles, Tamas, Matyas, Bringas, John, Park, John W, Berger, Mitchel S, Bankiewicz, Krystof
• Format: Journal Article
• Language: English
• Published: United States 01.11.2005
• Subjects: Animals; Brain; Carbocyanines - pharmacokinetics; Catheterization - instrumentation; Coloring Agents - pharmacokinetics; Convection; Drug Delivery Systems - instrumentation; Fluorescent Dyes - pharmacokinetics; Gels; Liposomes - pharmacokinetics; Macaca fascicularis; Male; Rats; Rats, Sprague-Dawley; Sepharose; Trypan Blue - pharmacokinetics
• ISSN: 0022-3085
• DOI: 10.3171/jns.2005.103.5.0923

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. 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 microl/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macacafascicularis) 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-microl/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. 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.