Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy

Ischemic stroke is the most common type of stroke and thrombolytic therapy is the only approved treatment. However, current thrombolytic therapy with tissue plasminogen activator (tPA) is often hampered by the increased risk of hemorrhage. Plasmin, a direct fibrinolytic, has a significantly superior...

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Autores principales:	Ramsha Aamir, Cameron Fyffe, Netanel Korin, Daniel A. Lawrence, Enming J. Su, Mathumai Kanapathipillai
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	plasmin nanoformulation ischemic stroke fibrinolysis heparin Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e7af1584984b4c5993114a2c6b019efb
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spelling	oai:doaj.org-article:e7af1584984b4c5993114a2c6b019efb2021-11-11T16:56:34ZHeparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy10.3390/ijms2221114771422-00671661-6596https://doaj.org/article/e7af1584984b4c5993114a2c6b019efb2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11477https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Ischemic stroke is the most common type of stroke and thrombolytic therapy is the only approved treatment. However, current thrombolytic therapy with tissue plasminogen activator (tPA) is often hampered by the increased risk of hemorrhage. Plasmin, a direct fibrinolytic, has a significantly superior hemostatic safety profile; however, if injected intravenously it becomes rapidly inactivated by anti-plasmin. Nanoformulations have been shown to increase drug stability and half-life and hence could be applied to increase the plasmin therapeutic efficacy. Here in this paper, we report a novel heparin and arginine-based plasmin nanoformulation that exhibits increased plasmin stability and efficacy. In vitro studies revealed significant plasmin stability in the presence of anti-plasmin and efficient fibrinolytic activity. In addition, these particles showed no significant toxicity or oxidative stress effects in human brain microvascular endothelial cells, and no significant blood brain barrier permeability. Further, in a mouse photothrombotic stroke model, plasmin nanoparticles exhibited significant efficacy in reducing stroke volume without overt intracerebral hemorrhage (ICH) compared to free plasmin treatment. The study shows the potential of a plasmin nanoformulation in ischemic stroke therapy.Ramsha AamirCameron FyffeNetanel KorinDaniel A. LawrenceEnming J. SuMathumai KanapathipillaiMDPI AGarticleplasminnanoformulationischemic strokefibrinolysisheparinBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11477, p 11477 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	plasmin nanoformulation ischemic stroke fibrinolysis heparin Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	plasmin nanoformulation ischemic stroke fibrinolysis heparin Biology (General) QH301-705.5 Chemistry QD1-999 Ramsha Aamir Cameron Fyffe Netanel Korin Daniel A. Lawrence Enming J. Su Mathumai Kanapathipillai Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy
description	Ischemic stroke is the most common type of stroke and thrombolytic therapy is the only approved treatment. However, current thrombolytic therapy with tissue plasminogen activator (tPA) is often hampered by the increased risk of hemorrhage. Plasmin, a direct fibrinolytic, has a significantly superior hemostatic safety profile; however, if injected intravenously it becomes rapidly inactivated by anti-plasmin. Nanoformulations have been shown to increase drug stability and half-life and hence could be applied to increase the plasmin therapeutic efficacy. Here in this paper, we report a novel heparin and arginine-based plasmin nanoformulation that exhibits increased plasmin stability and efficacy. In vitro studies revealed significant plasmin stability in the presence of anti-plasmin and efficient fibrinolytic activity. In addition, these particles showed no significant toxicity or oxidative stress effects in human brain microvascular endothelial cells, and no significant blood brain barrier permeability. Further, in a mouse photothrombotic stroke model, plasmin nanoparticles exhibited significant efficacy in reducing stroke volume without overt intracerebral hemorrhage (ICH) compared to free plasmin treatment. The study shows the potential of a plasmin nanoformulation in ischemic stroke therapy.
format	article
author	Ramsha Aamir Cameron Fyffe Netanel Korin Daniel A. Lawrence Enming J. Su Mathumai Kanapathipillai
author_facet	Ramsha Aamir Cameron Fyffe Netanel Korin Daniel A. Lawrence Enming J. Su Mathumai Kanapathipillai
author_sort	Ramsha Aamir
title	Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy
title_short	Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy
title_full	Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy
title_fullStr	Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy
title_full_unstemmed	Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy
title_sort	heparin and arginine based plasmin nanoformulation for ischemic stroke therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e7af1584984b4c5993114a2c6b019efb
work_keys_str_mv	AT ramshaaamir heparinandargininebasedplasminnanoformulationforischemicstroketherapy AT cameronfyffe heparinandargininebasedplasminnanoformulationforischemicstroketherapy AT netanelkorin heparinandargininebasedplasminnanoformulationforischemicstroketherapy AT danielalawrence heparinandargininebasedplasminnanoformulationforischemicstroketherapy AT enmingjsu heparinandargininebasedplasminnanoformulationforischemicstroketherapy AT mathumaikanapathipillai heparinandargininebasedplasminnanoformulationforischemicstroketherapy
_version_	1718432209688330240

Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy

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