Limits...
Tissue plasminogen activator-based clot busting: Controlled delivery approaches.

El-Sherbiny IM, Elkholi IE, Yacoub MH - Glob Cardiol Sci Pract (2014)

Bottom Line: Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences.The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair.This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches.

View Article: PubMed Central - PubMed

Affiliation: Zewail City of Science and Technology, Center for Materials Science, University of Science and Technology, 6th October City, 12588 Giza, Egypt.

ABSTRACT
Cardiovascular diseases are the leading cause of death worldwide. Thrombosis, the formation of blood clot (thrombus) in the circulatory system obstructing the blood flow, is one of the main causes behind various ischemic arterial syndromes such as ischemic stroke and myocardial infarction, as well as vein syndromes such as deep vein thrombosis, and consequently, pulmonary emboli. Several thrombolytic agents have been developed for treating thrombosis, the most common being tissue plasminogen activator (tPA), administrated systemically or locally via IV infusion directly proximal to the thrombus, with the aim of restoring and improving the blood flow. TPA triggers the dissolution of thrombi by inducing the conversion of plasminogen to protease plasmin followed by fibrin digestion that eventually leads to clot lysis. Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences. The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair. This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches.

No MeSH data available.


Related in: MedlinePlus

An illustration of the stages of thrombosis.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4352685&req=5

fig2: An illustration of the stages of thrombosis.

Mentions: Thrombosis takes place in two stages, primary hemostasis, and secondary hemostasis (Figure 2).3 Primary hemostasis is initiated by platelets' adherence to the damaged vascular endothelium, in a complex involving multiple platelet membrane receptors, to form a platelet plug.4 Secondary hemostasis includes the activation of the coagulation system, which finally leads to conversion of fibrinogen into fibrin to form a hemostatic clot.5 Platelet adhesion to the endothelium via the GP Ib receptor and von Willebrand factor (VWF) is followed by platelet activation (in the form of shape changes in the platelet, release of thromboxane A2, serotonin and other agents, and expression of GP IIb/ IIIa receptors on platelets' surface). The final step is binding of fibrinogen and VWF to the activated GP IIb/ IIIa receptors of two platelets, creating a growing aggregate.3,6


Tissue plasminogen activator-based clot busting: Controlled delivery approaches.

El-Sherbiny IM, Elkholi IE, Yacoub MH - Glob Cardiol Sci Pract (2014)

An illustration of the stages of thrombosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352685&req=5

fig2: An illustration of the stages of thrombosis.
Mentions: Thrombosis takes place in two stages, primary hemostasis, and secondary hemostasis (Figure 2).3 Primary hemostasis is initiated by platelets' adherence to the damaged vascular endothelium, in a complex involving multiple platelet membrane receptors, to form a platelet plug.4 Secondary hemostasis includes the activation of the coagulation system, which finally leads to conversion of fibrinogen into fibrin to form a hemostatic clot.5 Platelet adhesion to the endothelium via the GP Ib receptor and von Willebrand factor (VWF) is followed by platelet activation (in the form of shape changes in the platelet, release of thromboxane A2, serotonin and other agents, and expression of GP IIb/ IIIa receptors on platelets' surface). The final step is binding of fibrinogen and VWF to the activated GP IIb/ IIIa receptors of two platelets, creating a growing aggregate.3,6

Bottom Line: Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences.The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair.This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches.

View Article: PubMed Central - PubMed

Affiliation: Zewail City of Science and Technology, Center for Materials Science, University of Science and Technology, 6th October City, 12588 Giza, Egypt.

ABSTRACT
Cardiovascular diseases are the leading cause of death worldwide. Thrombosis, the formation of blood clot (thrombus) in the circulatory system obstructing the blood flow, is one of the main causes behind various ischemic arterial syndromes such as ischemic stroke and myocardial infarction, as well as vein syndromes such as deep vein thrombosis, and consequently, pulmonary emboli. Several thrombolytic agents have been developed for treating thrombosis, the most common being tissue plasminogen activator (tPA), administrated systemically or locally via IV infusion directly proximal to the thrombus, with the aim of restoring and improving the blood flow. TPA triggers the dissolution of thrombi by inducing the conversion of plasminogen to protease plasmin followed by fibrin digestion that eventually leads to clot lysis. Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences. The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair. This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches.

No MeSH data available.


Related in: MedlinePlus