Long-Term Biocompatibility of NanoGATE Drug Delivery Implant

Autor: Teri West, Michael Cohen, Sadhana Sharma, Anthony A. Boiarski, Robbie J. Walczak, Kristie Melnik, Mauro Ferrari, John P. Shapiro
Rok vydání: 2005
Předmět:
Zdroj: Nanobiotechnology. 1:035-042
ISSN: 1551-1286
DOI: 10.1385/nbt:1:1:035
Popis: 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.
Databáze: OpenAIRE