Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Re...

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Autores principales:	Jain PP, Leber R, Nagaraj C, Leitinger G, Lehofer B, Olschewski H, Olschewski A, Prassl R, Marsh LM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6dbf530d43774c399bd3f5e19398ee19
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spelling	oai:doaj.org-article:6dbf530d43774c399bd3f5e19398ee192021-12-02T03:55:35ZLiposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries1178-2013https://doaj.org/article/6dbf530d43774c399bd3f5e19398ee192014-07-01T00:00:00Zhttp://www.dovepress.com/liposomal-nanoparticles-encapsulating-iloprost-exhibit-enhanced-vasodi-a17506https://doaj.org/toc/1178-2013 Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.Keywords: prostacyclin, cationic liposomes, pulmonary hypertension, wire myographJain PPLeber RNagaraj CLeitinger GLehofer BOlschewski HOlschewski APrassl RMarsh LMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3249-3261 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Jain PP Leber R Nagaraj C Leitinger G Lehofer B Olschewski H Olschewski A Prassl R Marsh LM Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
description	Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.Keywords: prostacyclin, cationic liposomes, pulmonary hypertension, wire myograph
format	article
author	Jain PP Leber R Nagaraj C Leitinger G Lehofer B Olschewski H Olschewski A Prassl R Marsh LM
author_facet	Jain PP Leber R Nagaraj C Leitinger G Lehofer B Olschewski H Olschewski A Prassl R Marsh LM
author_sort	Jain PP
title	Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
title_short	Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
title_full	Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
title_fullStr	Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
title_full_unstemmed	Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
title_sort	liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/6dbf530d43774c399bd3f5e19398ee19
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_version_	1718401556211040256

Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

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