Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting

Nour Shobaki,* Yusuke Sato,* Hideyoshi Harashima Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan *These authors contributed equally to this work Introduction: The development of targeted drug delivery systems is a...

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Autores principales:	Shobaki N, Sato Y, Harashima H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	acid dissociation constant liver sinusoidal endothelial cells physical targeting short interfering RNA Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/02c4f4f3bbe34fdc89765534683a7a87
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spelling	oai:doaj.org-article:02c4f4f3bbe34fdc89765534683a7a872021-12-02T05:47:02ZMixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting1178-2013https://doaj.org/article/02c4f4f3bbe34fdc89765534683a7a872018-12-01T00:00:00Zhttps://www.dovepress.com/mixing-lipids-to-manipulate-the-ionization-status-of-lipid-nanoparticl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Nour Shobaki,* Yusuke Sato,* Hideyoshi Harashima Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan *These authors contributed equally to this work Introduction: The development of targeted drug delivery systems is a rapidly growing area in the field of nanomedicine. Methods: We report herein on optimizing the targeting efficiency of a lipid nanoparticle (LNP) by manipulating the acid dissociation constant (pKa) value of its membrane, which reflects its ionization status. Instead of changing the chemical structure of the lipids to achieve this, we used a mixture of two types of pH-sensitive cationic lipids that show different pKa values in a single LNP. We mixed various ratios of YSK05 and YSK12-C4 lipids, which have pKa values of 6.50 and 8.00, respectively, in one formulation (referred to as YSK05/12-LNP). Results: The pKa of the YSK05/12-LNP was dependent not only on the molar ratio of each lipid but also on the individual contribution of each lipid to the final pKa (the YSK12-C4 lipid showed a higher contribution). Furthermore, we succeeded in targeting and delivering short interfering RNA to liver sinusoidal endothelial cells using one of the YSK05/12-LNPs which showed an optimum pKa value of 7.15 and an appropriate ionization status (~36% cationic charge) to permit the particles to be taken up by liver sinusoidal endothelial cells. Conclusion: This strategy has the potential for preparing custom LNPs with endless varieties of structures and final pKa values, and would have potential applications in drug delivery and ionic-based tissue targeting. Keywords: acid dissociation constant, liver sinusoidal endothelial cells, physical targeting, short interfering RNAShobaki NSato YHarashima HDove Medical Pressarticleacid dissociation constantliver sinusoidal endothelial cellsphysical targetingshort interfering RNAMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8395-8410 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	acid dissociation constant liver sinusoidal endothelial cells physical targeting short interfering RNA Medicine (General) R5-920
spellingShingle	acid dissociation constant liver sinusoidal endothelial cells physical targeting short interfering RNA Medicine (General) R5-920 Shobaki N Sato Y Harashima H Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
description	Nour Shobaki,* Yusuke Sato,* Hideyoshi Harashima Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan *These authors contributed equally to this work Introduction: The development of targeted drug delivery systems is a rapidly growing area in the field of nanomedicine. Methods: We report herein on optimizing the targeting efficiency of a lipid nanoparticle (LNP) by manipulating the acid dissociation constant (pKa) value of its membrane, which reflects its ionization status. Instead of changing the chemical structure of the lipids to achieve this, we used a mixture of two types of pH-sensitive cationic lipids that show different pKa values in a single LNP. We mixed various ratios of YSK05 and YSK12-C4 lipids, which have pKa values of 6.50 and 8.00, respectively, in one formulation (referred to as YSK05/12-LNP). Results: The pKa of the YSK05/12-LNP was dependent not only on the molar ratio of each lipid but also on the individual contribution of each lipid to the final pKa (the YSK12-C4 lipid showed a higher contribution). Furthermore, we succeeded in targeting and delivering short interfering RNA to liver sinusoidal endothelial cells using one of the YSK05/12-LNPs which showed an optimum pKa value of 7.15 and an appropriate ionization status (~36% cationic charge) to permit the particles to be taken up by liver sinusoidal endothelial cells. Conclusion: This strategy has the potential for preparing custom LNPs with endless varieties of structures and final pKa values, and would have potential applications in drug delivery and ionic-based tissue targeting. Keywords: acid dissociation constant, liver sinusoidal endothelial cells, physical targeting, short interfering RNA
format	article
author	Shobaki N Sato Y Harashima H
author_facet	Shobaki N Sato Y Harashima H
author_sort	Shobaki N
title	Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
title_short	Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
title_full	Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
title_fullStr	Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
title_full_unstemmed	Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
title_sort	mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/02c4f4f3bbe34fdc89765534683a7a87
work_keys_str_mv	AT shobakin mixinglipidstomanipulatetheionizationstatusoflipidnanoparticlesforspecifictissuetargeting AT satoy mixinglipidstomanipulatetheionizationstatusoflipidnanoparticlesforspecifictissuetargeting AT harashimah mixinglipidstomanipulatetheionizationstatusoflipidnanoparticlesforspecifictissuetargeting
_version_	1718400211832799232

Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting

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