A Novel Retrievable Drug Infusion Stent and Blood-Brain Barrier Portal for Antibody Therapies to the Spinal Cord.

Background and objectives: The blood-brain barrier (BBB) is prohibitive to intravascular drug delivery. We hypothesized that isolation of spinal cord perfusion would focus on a higher effective dose while minimizing systemic toxicity and that a histamine portal would increase BBB permeability and facilitate large molecule therapies to the spinal cord.

Methods: A dumbbell-shaped, retrievable drug infusion stentgraft (RDIS) was constructed from nitinol and polytetrafluorethylene. A porcine model under anesthesia underwent percutaneous femoral insertion of the sheathed RDIS and deployment in the lower thoracic aorta by sheath withdrawal. Antiglial fibrillary acidic protein (GFAP) tracer antibody was instilled to the outer chamber for 30 minutes +/- 80 μg of histamine, followed by stent recovery by sheath advancement, staining of spinal cord with fluorescent secondary antibody, and measurement of mean fluorescence intensity.

Results: Angiography confirmed center lumen distal perfusion while an integrated cannula allowed infusion to the isolated outer chamber and intercostals. Although 80 μg of histamine delivered intravenously decreased the mean arterial pressure by 22 mm Hg briefly but significantly (P = .002), histamine infused into the RDIS outer chamber did not exhibit hypotensive effect. Animals treated using RDIS + histamine + GFAP (n = 5) revealed increased mean fluorescence intensity (mean 1074 ± 199) compared with either RDIS + GFAP without histamine (n = 5; 792 ± 223, P < .002) or simple IV infusion of GFAP + histamine (n = 5; 748 ± 172, P < .001). Although the stent perfused only 2-3 sets of intercostals, positive staining was observed well into the adjacent upper thoracic and lumbar spinal cord.

Conclusion: An RDIS achieves focal drug delivery of antibody to the spinal cord and is retrievable after use, whereas a histamine portal facilitates passage across the BBB. The RDIS may have future utility for vascular-based delivery of antibody therapeutics or other macromolecules focused to the spinal cord for oncological, spinal cord injury and neurodegenerative disease.