Long-term biocompatibility of NanoGATE drug delivery implant |
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Authors: | Robbie J Walczak Anthony Boiarski Michael Cohen Teri West Kristie Melnik John Shapiro Sadhana Sharma Mauro Ferrari |
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Institution: | (1) iMEDD, Inc., 1381 Kinnear Rd., Suite 111, 43212 Columbus, OH, USA;(2) Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, 473 West 12th Avenue, 43210 Columbus, OH, USA;(3) Department of Internal Medicine, Division of Hematology and Oncology, The Ohio State University, 43210 Columbus, OH, USA |
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Abstract: | The fouling of components and the formation of a fibrotic tissue capsule around subcutaneously implanted medical devices are
two major obstacles in developing viable, long-term implantable drug delivery systems. NanoGATE is a subcutaneous implant
designed for constant-output passive diffusion of a drug of interest through a silicon nanopore membrane. To this end, we
have investigated the long-term in vivo biocompatibility of the NanoGATE implant in terms of the fouling of the nanopore membrane
and the formation of a fibrotic tissue capsule around the implant. We have also evaluated how these effects influence diffusion
of a lysozyme surrogate from the device once implanted within the vascular compartment of a Sprague-Dawley rat model. Using
several model biomolecules such as glucose, lysozyme, and albumin, our studies suggest that silicon nanopore membranes do
not foul when implanted subcutaneously for 6 mo. This study also reveals the tissue capsule that naturally forms around the
implant does not limit diffusion of molecules with molecular weights on the order of 14.4 kDa at therapeutic delivery rates
of tens of micrograms per day. This indicates that our NanoGATE implant should be completely functional in vivo, providing
constant release levels of a drug over an extended time period. Thus, by adjusting the release rate to fit the pharmacokinetic
clearance profile of the Sprague-Dawley rat, long-term steady-state blood plasma concentrations can be achieved. |
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Keywords: | Silicon nanopore membrane NanoGATE biocompatibility drug delivery implant |
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