In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis

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Publication Type Journal Article
School or College College of Pharmacy
Department Pharmacology & Toxicology
Creator Blumenthal, Donald K.
Other Author Terry, Christi M.; Li, Li; Li, Huan; Zhuplatov, Ilya; Kim, Seong-Eun; Owen, Shawn C.; Kholmovski, Eugene G.; Fowers, Kirk D.; Rathi, Ramesh; Cheung, Alfred K.
Title In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis
Date 2012-01-01
Description Synthetic arteriovenous (AV) hemodialysis grafts are plagued by hyperplasia resulting in occlusion and graft failure yet there are no clinically available preventative treatments. Here the delivery and degradation of a sirolimus-laden polymer gel were monitored in vivo by magnetic resonance imaging (MRI) and its efficacy for inhibiting hyperplasia was evaluated in a porcine model of AV graft stenosis. Synthetic grafts were placed between the carotid artery and ipsilateral jugular vein of swine. A biodegradable polymer gel loaded with sirolimus (2.5 mg/mL) was immediately applied perivascularly to the venous anastomosis, and reapplied by ultrasound-guided injections at one, two and three weeks. Control grafts received neither sirolimus nor polymer. The lumen cross-sectional area at the graft-vein anastomosis was assessed in vivo by non-invasive MRI. The explanted tissues also underwent histological analysis. A specifically developed MRI pulse sequence provided a high contrast-to-noise ratio (CNR) between the polymer and surrounding tissue that allowed confirmation of gel location after injection. Polymer signal decreased up to 80% at three to four weeks after injection, slightly faster than its degradation kinetics in vitro. The MR image of the polymer was confirmed by visual assessment at necropsy. On histological assessment, the mean hyperplasia surface area of the treated graftwas 52% lower than that of the control grafts (0.43 mm2 vs. 0.89mm2; pb0.003), while the minimum cross-sectional lumen area, as measured on MRI, was doubled (5.3mm2 vs 2.5 mm2; pb0.05).
Type Text
Publisher Elsevier
Volume 160
Issue 3
First Page 459
Last Page 467
DOI http://dx.doi.org/DOI: 10.1016/j.jconrel.2012.03.011.
Dissertation Institution University of Utah
Language eng
Bibliographic Citation Terry, C. M., Li, L., Li, H., Zhuplatov, I., Blumenthal, D. K., Kim, S.-E., Owen, S. C., Kholmovski, E. G., Fowers, K. D., Rathi, R., & Cheung, A. K. (2012). In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis. Journal of Controlled Release, 160(3), 459-67.
Rights Management (c) Elsevier ; Reprinted from Terry, C. M., Li, L., Li, H., Zhuplatov, I., Blumenthal, D. K., Kim, S.-E., Owen, S. C., Kholmovski, E. G., Fowers, K. D., Rathi, R., & Cheung, A. K. (2012). In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis. Journal of Controlled Release.
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Identifier uspace,17307
ARK ark:/87278/s6xd1kdt
Setname ir_uspace
Date Created 2012-07-31
Date Modified 2012-08-16
ID 707938
Reference URL https://collections.lib.utah.edu/ark:/87278/s6xd1kdt
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