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

I must be missing something here, if the artery is blocked then blood wouldn't be flowing there resulting in no shear forces at all.

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

Molloy C, Yao Y, Kammoun H, Bonnard T, Hoefer T, Alt K, Tovar-Lopez F, Rosengarten G, Ramsland P, van der Meer A, van den Berg A, Murphy A, Hagemeyer C, Peter K, Westein E; Journal of Thrombosis and Haemostasis (Mar 2017)

Tags:

• eptifibatide
• phosphatidyl choline
• Pregnancy
• Thrombosis

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BACKGROUND Myocardial infarction and stroke remain the leading causes of mortality and morbidity. The major limitation of current antiplatelet therapy is that their effective concentrations are limited due to bleeding complications. Targeted delivery of antiplatelet drug to sites of thrombosis would overcome these limitations.
OBJECTIVES Here, we have exploited a key biomechanical feature specific to thrombosis; significantly increased blood shear stress due to a reduction in the lumen of the vessel, to achieve site directed delivery of the clinically used antiplatelet agent eptifibatide using shear-sensitive phosphatidylcholine based nanocapsules.
METHODS 2.8x10(12) PC based nanocapsules with high dose encapsulated eptifibatide were introduced in microfluidic blood perfusion assays and in in vivo models of thrombosis and tail bleeding.
RESULTS Shear-triggered nanocapsule delivery of eptifibatide inhibited in vitro thrombus formation selectively under stenotic and high shear flow conditions above 1,000 s(-1) shear rate while leaving thrombus formation under physiological 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 display 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. This article is protected by copyright. All rights reserved.