N. Vyavahare, N. A. Scott, S. Hanson
Nov 1, 1993
Citations
0
Influential Citations
5
Citations
Quality indicators
Journal
Journal of Controlled Release
Abstract
Abstract d -Phenylalanyl- l -prolyl- l -arginyl chloromethyl ketone (PPACK) was incorporated into thin films of ethylene vinyl acetate copolymer (EVA, 33% vinyl acetate content). The release devices sustained the release of PPACK for approximately 120 min and delivered approximately 47 μg of PPACK/cm 2 /h in vitro at 4°C. The chemical degradation of PPACK was evaluated by HPLC and by 1 H-NMR spectroscopy. In spite of its low chemical stability, PPACK could be released from the polymeric matrix without apparent degradation. As a functional test of the release of PPACK from a polymer, the ability to inhibit platelet deposition on a metallic coronary stent was tested in vivo in a clinically relevant baboon model. In control experiments, the stent itself as well as stents in contact with plain films of EVA were found to be highly thrombogenic. However, when the coronary stent was placed in contact with a polymer film loaded with PPACK, there was a marked diminution in the number of platelets deposited on the stent for the duration of the 2-h experiment. Those studies provide the first experimental confirmation of the concept that the intraarterial, site-specific release of a thrombin inhibitor can reduce platelet deposition on an artificial polymeric surface in vivo.