Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Hyunggun Kim,1 George L Britton,1 Tao Peng,1 Christy K Holland,2 David D McPherson,1 Shao-Ling Huang1 1Division of Cardiovascular Medicine, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA; 2Division of Cardiovascular Diseases, Department o...

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Autores principales:	Kim H, Britton GL, Peng T, Holl, CK, McPherson DD, Huang SL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c71039c8f20a427eb7ed1728b7607863
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spelling	oai:doaj.org-article:c71039c8f20a427eb7ed1728b76078632021-12-02T11:07:29ZNitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage1178-2013https://doaj.org/article/c71039c8f20a427eb7ed1728b76078632013-12-01T00:00:00Zhttp://www.dovepress.com/nitric-oxide-loaded-echogenic-liposomes-for-treatment-of-vasospasm-fol-a15354https://doaj.org/toc/1178-2013 Hyunggun Kim,1 George L Britton,1 Tao Peng,1 Christy K Holland,2 David D McPherson,1 Shao-Ling Huang1 1Division of Cardiovascular Medicine, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA; 2Division of Cardiovascular Diseases, Department of Internal Medicine, and Department of Biomedical Engineering and Radiology, University of Cincinnati, Cincinnati, OH, USA Abstract: Delayed cerebral vasospasm following subarachnoid hemorrhage causes severe ischemic neurologic deficits leading to permanent neurologic dysfunction or death. Reduced intravascular and perivascular nitric oxide (NO) availability is a primary pathophysiology of cerebral vasospasm. In this study, we evaluated NO-loaded echogenic liposomes (NO-ELIP) for ultrasound-facilitated NO delivery to produce vasodilation for treatment of vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP both ex vivo and in vivo. Liposomes containing phospholipids and cholesterol were prepared, and NO was encapsulated. The encapsulation and release of NO from NO-ELIP were determined by the syringe/vacuum method and ultrasound imaging. The ex vivo vasodilative effect of NO-ELIP was investigated using rabbit carotid arteries. Arterial vasodilation was clearly observed with NO-ELIP exposed to Doppler ultrasound whereas there was little vasodilative effect without exposure to Doppler ultrasound in the presence of red blood cells. Penetration of NO into the arterial wall was determined by fluorescent microscopy. The vasodilative effects of intravenously administered NO-ELIP in vivo were determined in a rat subarachnoid hemorrhage model. NO-ELIP with ultrasound activation over the carotid artery demonstrated effective arterial vasodilation in vivo resulting in improved neurologic function. This novel methodology for ultrasound-controlled delivery of NO has the potential for therapeutic treatment of vasospasm following subarachnoid hemorrhage. This ultrasound-controlled release strategy provides a new avenue for targeted bioactive gas and therapeutic delivery for improved stroke treatment. Keywords: vasospasm, vasodilation, subarachnoid hemorrhage, nitric oxide, liposomes, ultrasoundKim HBritton GLPeng THollCKMcPherson DDHuang SLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 155-165 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kim H Britton GL Peng T Holl CK McPherson DD Huang SL Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
description	Hyunggun Kim,1 George L Britton,1 Tao Peng,1 Christy K Holland,2 David D McPherson,1 Shao-Ling Huang1 1Division of Cardiovascular Medicine, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA; 2Division of Cardiovascular Diseases, Department of Internal Medicine, and Department of Biomedical Engineering and Radiology, University of Cincinnati, Cincinnati, OH, USA Abstract: Delayed cerebral vasospasm following subarachnoid hemorrhage causes severe ischemic neurologic deficits leading to permanent neurologic dysfunction or death. Reduced intravascular and perivascular nitric oxide (NO) availability is a primary pathophysiology of cerebral vasospasm. In this study, we evaluated NO-loaded echogenic liposomes (NO-ELIP) for ultrasound-facilitated NO delivery to produce vasodilation for treatment of vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP both ex vivo and in vivo. Liposomes containing phospholipids and cholesterol were prepared, and NO was encapsulated. The encapsulation and release of NO from NO-ELIP were determined by the syringe/vacuum method and ultrasound imaging. The ex vivo vasodilative effect of NO-ELIP was investigated using rabbit carotid arteries. Arterial vasodilation was clearly observed with NO-ELIP exposed to Doppler ultrasound whereas there was little vasodilative effect without exposure to Doppler ultrasound in the presence of red blood cells. Penetration of NO into the arterial wall was determined by fluorescent microscopy. The vasodilative effects of intravenously administered NO-ELIP in vivo were determined in a rat subarachnoid hemorrhage model. NO-ELIP with ultrasound activation over the carotid artery demonstrated effective arterial vasodilation in vivo resulting in improved neurologic function. This novel methodology for ultrasound-controlled delivery of NO has the potential for therapeutic treatment of vasospasm following subarachnoid hemorrhage. This ultrasound-controlled release strategy provides a new avenue for targeted bioactive gas and therapeutic delivery for improved stroke treatment. Keywords: vasospasm, vasodilation, subarachnoid hemorrhage, nitric oxide, liposomes, ultrasound
format	article
author	Kim H Britton GL Peng T Holl CK McPherson DD Huang SL
author_facet	Kim H Britton GL Peng T Holl CK McPherson DD Huang SL
author_sort	Kim H
title	Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
title_short	Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
title_full	Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
title_fullStr	Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
title_full_unstemmed	Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
title_sort	nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/c71039c8f20a427eb7ed1728b7607863
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Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

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