Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles

Yongxue Zhao, Long Wang, Mina Yan, Yanling Ma, Guangxi Zang, Zhennan She, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People&rsquo;s Republic of ChinaAbstract: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG),...

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Autores principales:	Zhao Y, Wang L, Yan M, Ma Y, Zang G, She Z, Deng Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/43764787ca884a29b964e5e0fde9649d
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spelling	oai:doaj.org-article:43764787ca884a29b964e5e0fde9649d2021-12-02T02:42:09ZRepeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles1176-91141178-2013https://doaj.org/article/43764787ca884a29b964e5e0fde9649d2012-06-01T00:00:00Zhttp://www.dovepress.com/repeated-injection-of-pegylated-solid-lipid-nanoparticles-induces-acce-a10086https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yongxue Zhao, Long Wang, Mina Yan, Yanling Ma, Guangxi Zang, Zhennan She, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People&rsquo;s Republic of ChinaAbstract: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG), known as PEGylation, is regarded as a major breakthrough in the application of nanocarriers. However, PEGylated nanocarriers (including liposomes and polymeric nanoparticles) induce what is referred to as the &ldquo;accelerated blood clearance (ABC) phenomenon&rdquo; upon repeated injection and consequently they lose their sustained circulation characteristics. Despite this, the present authors are not aware of any reports of accelerated clearance due to repeated injection for PEGylated solid lipid nanoparticles (SLNs), another promising nanocarrier. This study investigated the pharmacokinetics of PEGylated SLNs upon repeated administration in mice; moreover, the impact of circulation time on the induction of the ABC phenomenon was studied in beagles for the first time. The ABC index, selected as the ratio of the area under the concentration-time curve from time 0 to the last measured concentration of a second injection to that of the first injection, was used to evaluate the extent of this phenomenon. Results showed that the PEGylated SLNs exhibited accelerated clearance from systemic circulation upon repeated injection, both in mice and in beagles, and the ratio for the different time intervals, which showed that the ABC index exhibited significant difference within 30 minutes following the second injection, was good enough to evaluate the magnitude of ABC. This ABC index indicated that the 10 mol% PEG SLNs with a suitable prolonged circulation time induced the most marked ABC phenomenon in this research. This study demonstrated that, like PEGylated nanocarriers such as liposomes and polymeric nanoparticles, PEGylated SLNs induced the ABC phenomenon upon repeated injection &ndash; the beagle was a valuable experimental animal for this research. Furthermore, the authors considered that a relatively extended circulation time of the initial dose may be the underlying major factor determining the induction of the ABC phenomenon.Keywords: SLNs, polyethylene glycol, ABC phenomenon, circulation timeZhao YWang LYan MMa YZang GShe ZDeng YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2891-2900 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhao Y Wang L Yan M Ma Y Zang G She Z Deng Y Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
description	Yongxue Zhao, Long Wang, Mina Yan, Yanling Ma, Guangxi Zang, Zhennan She, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People&rsquo;s Republic of ChinaAbstract: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG), known as PEGylation, is regarded as a major breakthrough in the application of nanocarriers. However, PEGylated nanocarriers (including liposomes and polymeric nanoparticles) induce what is referred to as the &ldquo;accelerated blood clearance (ABC) phenomenon&rdquo; upon repeated injection and consequently they lose their sustained circulation characteristics. Despite this, the present authors are not aware of any reports of accelerated clearance due to repeated injection for PEGylated solid lipid nanoparticles (SLNs), another promising nanocarrier. This study investigated the pharmacokinetics of PEGylated SLNs upon repeated administration in mice; moreover, the impact of circulation time on the induction of the ABC phenomenon was studied in beagles for the first time. The ABC index, selected as the ratio of the area under the concentration-time curve from time 0 to the last measured concentration of a second injection to that of the first injection, was used to evaluate the extent of this phenomenon. Results showed that the PEGylated SLNs exhibited accelerated clearance from systemic circulation upon repeated injection, both in mice and in beagles, and the ratio for the different time intervals, which showed that the ABC index exhibited significant difference within 30 minutes following the second injection, was good enough to evaluate the magnitude of ABC. This ABC index indicated that the 10 mol% PEG SLNs with a suitable prolonged circulation time induced the most marked ABC phenomenon in this research. This study demonstrated that, like PEGylated nanocarriers such as liposomes and polymeric nanoparticles, PEGylated SLNs induced the ABC phenomenon upon repeated injection &ndash; the beagle was a valuable experimental animal for this research. Furthermore, the authors considered that a relatively extended circulation time of the initial dose may be the underlying major factor determining the induction of the ABC phenomenon.Keywords: SLNs, polyethylene glycol, ABC phenomenon, circulation time
format	article
author	Zhao Y Wang L Yan M Ma Y Zang G She Z Deng Y
author_facet	Zhao Y Wang L Yan M Ma Y Zang G She Z Deng Y
author_sort	Zhao Y
title	Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
title_short	Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
title_full	Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
title_fullStr	Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
title_full_unstemmed	Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
title_sort	repeated injection of pegylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/43764787ca884a29b964e5e0fde9649d
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_version_	1718402213717475328

Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles

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