In vivo performance of a microfabricated catheter for intraparenchymal delivery

Martin L Brady, Raghu Raghavan, Deep Singh, P J Anand, Adam S Fleisher, Jaime Mata, William C Broaddus, William L Olbricht
Journal of Neuroscience Methods 2014 May 30, 229: 76-83

BACKGROUND: Convection-enhanced delivery (CED) is currently the only effective clinical technique to deliver biological therapeutic agents that would otherwise not cross the blood-brain barrier. Despite the promise of CED, several technical problems have limited its effectiveness.

NEW METHOD: Brain infusions into a large mammal (pig) were performed with a catheter that was fabricated using micro-electro-mechanical systems (MEMS) technology (Olbricht et al., 2010). The performance of the catheter was evaluated for infusions at increasing infusion rates. Magnetic resonance (MR) images were acquired in real time to examine the distribution of infused tracers in the parenchyma.

RESULTS: Both backflow and the distribution of CED of infusates into a variety of cytoarchitectures in porcine brain were quantified. Concentration profiles were determined for several MR contrast reagents as well as a fluorescent dye that are the sizes of small molecules, therapeutic proteins and an adeno-associated virus (AAV). The reagents can serve as surrogates for assessing the convective distribution of active molecules. Infusion rates up to 20μL/min were attained without evidence of backflow along the catheter.

COMPARISON WITH EXISTING METHODS: The device performed well in terms of both backflow and infusion, superior to that of many studies reported in the literature on other catheters. All infused molecules had comparable ratios of distribution to infusion volumes.

CONCLUSIONS: The catheter described in this report appears able to target tissue structures with precision, deliver therapeutics at high infusion rates, and resist backflow that can compromise the efficacy of CED therapy. The technology allows development of "smart" catheters for future applications.

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