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

Maybe your doctor can use this to remove the blood clots inside your blood vessels. 
http://www.docguide.com/shear-sensitive-nanocapsule-drug-release-site-specific-inhibition-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.

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

Read/Add Comments | Email This | Print This | PubMed

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.

Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

The video associated with this looks great. When do we get this in real life?  What is your doctor and hospital doing to get this validated? What about your stroke association doing ANYTHING AT ALL?
Video here:
https://www.facebook.com/ScienceNaturePage/videos/778434595622134/

Press release here:
http://wyss.harvard.edu/viewpressrelease/224/drugdevice-combination-opens-potential-new-path-to-treat-stroke

 Research article here:
Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

1. Miklos G. Marosfoi, MD*,
2. Netanel Korin, PhD*,
3. Matthew J. Gounis, PhD*,
4. Oktay Uzun, PhD,
5. Srinivasan Vedantham, PhD,
6. Erin T. Langan, BS,
7. Anne-Laure Papa, PhD,
8. Olivia W. Brooks,
9. Chris Johnson, BS,
10. Ajit S. Puri, MD,
11. Deen Bhatta, MS,
12. Mathumai Kanapathipillai, PhD,
13. Ben R. Bronstein, MD,
14. Ju-Yu Chueh, PhD,
15. Donald E. Ingber, MD, PhD† and
16. Ajay K. Wakhloo, MD, PhD†

+ Author Affiliations

1. From the New England Center for Stroke Research, Department of Radiology, University of Massachusetts, Worcester (M.G.M., M.J.G., S.V., E.T.L., O.W.B., A.S.P., J.-Y.C., A.K.W.); Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA (N.K., O.U., A.-L.P., C.J., D.B., M.K., B.R.B., D.E.I.); Department of Biomedical Engineering, Technion, Israel (N.K.); Vascular Biology Program, Boston Children’s Hospital and Harvard University, Boston, MA (D.E.I.); and Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA (D.E.I.).

1. Correspondence to Donald E. Ingber, MD, PhD, Wyss Institute at Harvard, CLSB5, 3 Blackfan Circle, Boston, MA 02115. E-mail don.ingber@wyss.harvard.edu

1. ↵* Drs Marosfoi, Korin, and Gounis contributed equally.
2. ↵† Drs Ingber and Wakhloo are joint senior authors.

Abstract

Background and Purpose—The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement.

Methods—A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy.

Results—Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001).

Conclusions—A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.