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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

Factors affecting hemostasis.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4352685&req=5

fig1: Factors affecting hemostasis.

Mentions: Hemostasis is a multifactorial state that ensures efficient blood flow through peripheral vascular districts. It is affected by the characteristics of blood vessel walls, platelets, the fibrinolytic system, and the coagulation pathway, which are all intimately related (Figure 1). All these factors function normally to produce an equilibrium between antithrombotic and prothrombotic factors.1,2 Any misbalance in this equilibrium will lead to thrombosis: the formation of a blood clot inside a vessel, causing its occlusion or stenosis, and leading to various clinical presentations, depending on the occluded vessel. For instance, cerebrovascular thrombosis will lead to stroke and coronary artery thrombosis will lead to ischemic heart diseases (angina or myocardial infarction).


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

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

Factors affecting hemostasis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Factors affecting hemostasis.
Mentions: Hemostasis is a multifactorial state that ensures efficient blood flow through peripheral vascular districts. It is affected by the characteristics of blood vessel walls, platelets, the fibrinolytic system, and the coagulation pathway, which are all intimately related (Figure 1). All these factors function normally to produce an equilibrium between antithrombotic and prothrombotic factors.1,2 Any misbalance in this equilibrium will lead to thrombosis: the formation of a blood clot inside a vessel, causing its occlusion or stenosis, and leading to various clinical presentations, depending on the occluded vessel. For instance, cerebrovascular thrombosis will lead to stroke and coronary artery thrombosis will lead to ischemic heart diseases (angina or myocardial infarction).

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