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Shear-sensitive nanocapsule drug release for site-specific inhibition of occlusive thrombus formation.

Molloy CP, Yao Y, Kammoun H, Bonnard T, Hoefer T, Alt K, Tovar-Lopez F, Rosengarten G, Ramsland PA, van der Meer AD, van den Berg A, Murphy AJ, Hagemeyer CE, Peter K, Westein E

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  • Journal Journal of thrombosis and haemostasis : JTH

  • Published 09 Apr 2017

  • Volume 15

  • ISSUE 5

  • Pagination 972-982

  • DOI 10.1111/jth.13666

Abstract

Essentials Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times. Local nanocapsule delivery of eptifibatide may be safer than systemic antiplatelet therapies.

while leaving thrombus formation under physiologic shear rates unaffected. Thrombosis was effectively prevented in in vivo models of vessel wall damage. Importantly, mice infused with shear-sensitive antiplatelet nanocapsules did not show prolonged bleeding times. Conclusions Targeted delivery of eptifibatide by shear-sensitive nanocapsules offers site-specific antiplatelet potential, and may form a basis for developing more potent and safer antiplatelet drugs.