Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization

Rebecca L Ball,1 Palak Bajaj,1,2 Kathryn A Whitehead1,2 1Department of Chemical Engineering, 2Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA Abstract: The broadest clinical application of siRNA therapeutics will be facilitated by drug-loaded delivery systems...

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Autores principales:	Ball RL, Bajaj P, Whitehead KA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Lipid nanoparticles nanoparticle stability lyophilization lyoprotectants nanoparticle storage siRNA delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f68eed9cf360479980e1cf98b0070882
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spelling	oai:doaj.org-article:f68eed9cf360479980e1cf98b00708822021-12-02T00:37:18ZAchieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization1178-2013https://doaj.org/article/f68eed9cf360479980e1cf98b00708822016-12-01T00:00:00Zhttps://www.dovepress.com/achieving-long-term-stability-of-lipid-nanoparticles-examining-the-eff-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Rebecca L Ball,1 Palak Bajaj,1,2 Kathryn A Whitehead1,2 1Department of Chemical Engineering, 2Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA Abstract: The broadest clinical application of siRNA therapeutics will be facilitated by drug-loaded delivery systems that maintain stability and potency for long times under ambient conditions. In the present study, we seek to better understand the stability and effect of storage conditions on lipidoid nanoparticles (LNPs), which have been previously shown by our group and others to potently deliver RNA to various cell and organ targets both in vitro and in vivo. Specifically, this study evaluates the influence of pH, temperature, and lyophilization on LNP efficacy in HeLa cells. When stored under aqueous conditions, we found that refrigeration (2°C) kept LNPs the most stable over 150 days compared to storage in the -20°C freezer or at room temperature. Because the pH of the storage buffer was not found to influence stability, it is suggested that the LNPs be stored under physiologically appropriate conditions (pH 7) for ease of use. Although aggregation and loss of efficacy were observed when LNPs were subjected to freeze–thaw cycles, their stability was retained with the use of the cryoprotectants, trehalose, and sucrose. Initially, lyophilization of the LNPs followed by reconstitution in aqueous buffer also led to reductions in efficacy, most likely due to aggregation upon reconstitution. Although the addition of ethanol to the reconstitution buffer restored efficacy, this approach is not ideal, as LNP solutions would require dialysis prior to use. Fortunately, we found that the addition of trehalose or sucrose to LNP solutions prior to lyophilization facilitated room temperature storage and reconstitution in aqueous buffer without diminishing delivery potency. Keywords: lipid nanoparticles, nanoparticle stability, lyophilization, lyoprotectants, nanoparticle storage, siRNA deliveryBall RLBajaj PWhitehead KADove Medical PressarticleLipid nanoparticlesnanoparticle stabilitylyophilizationlyoprotectantsnanoparticle storagesiRNA deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 305-315 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lipid nanoparticles nanoparticle stability lyophilization lyoprotectants nanoparticle storage siRNA delivery Medicine (General) R5-920
spellingShingle	Lipid nanoparticles nanoparticle stability lyophilization lyoprotectants nanoparticle storage siRNA delivery Medicine (General) R5-920 Ball RL Bajaj P Whitehead KA Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization
description	Rebecca L Ball,1 Palak Bajaj,1,2 Kathryn A Whitehead1,2 1Department of Chemical Engineering, 2Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA Abstract: The broadest clinical application of siRNA therapeutics will be facilitated by drug-loaded delivery systems that maintain stability and potency for long times under ambient conditions. In the present study, we seek to better understand the stability and effect of storage conditions on lipidoid nanoparticles (LNPs), which have been previously shown by our group and others to potently deliver RNA to various cell and organ targets both in vitro and in vivo. Specifically, this study evaluates the influence of pH, temperature, and lyophilization on LNP efficacy in HeLa cells. When stored under aqueous conditions, we found that refrigeration (2°C) kept LNPs the most stable over 150 days compared to storage in the -20°C freezer or at room temperature. Because the pH of the storage buffer was not found to influence stability, it is suggested that the LNPs be stored under physiologically appropriate conditions (pH 7) for ease of use. Although aggregation and loss of efficacy were observed when LNPs were subjected to freeze–thaw cycles, their stability was retained with the use of the cryoprotectants, trehalose, and sucrose. Initially, lyophilization of the LNPs followed by reconstitution in aqueous buffer also led to reductions in efficacy, most likely due to aggregation upon reconstitution. Although the addition of ethanol to the reconstitution buffer restored efficacy, this approach is not ideal, as LNP solutions would require dialysis prior to use. Fortunately, we found that the addition of trehalose or sucrose to LNP solutions prior to lyophilization facilitated room temperature storage and reconstitution in aqueous buffer without diminishing delivery potency. Keywords: lipid nanoparticles, nanoparticle stability, lyophilization, lyoprotectants, nanoparticle storage, siRNA delivery
format	article
author	Ball RL Bajaj P Whitehead KA
author_facet	Ball RL Bajaj P Whitehead KA
author_sort	Ball RL
title	Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization
title_short	Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization
title_full	Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization
title_fullStr	Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization
title_full_unstemmed	Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization
title_sort	achieving long-term stability of lipid nanoparticles: examining the effect of ph, temperature, and lyophilization
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/f68eed9cf360479980e1cf98b0070882
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Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization

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