Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming...

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Autores principales:	Zhang XW, Chen GJ, Zhang TP, Ma ZG, Wu BJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/30780422131b439ca9eb1c8c87439ead
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spelling	oai:doaj.org-article:30780422131b439ca9eb1c8c87439ead2021-12-02T04:21:09ZEffects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation1178-2013https://doaj.org/article/30780422131b439ca9eb1c8c87439ead2014-11-01T00:00:00Zhttp://www.dovepress.com/effects-of-pegylated-lipid-nanoparticles-on-the-oral-absorption-of-one-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanismZhang XWChen GJZhang TPMa ZGWu BJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5503-5514 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang XW Chen GJ Zhang TP Ma ZG Wu BJ Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation
description	Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanism
format	article
author	Zhang XW Chen GJ Zhang TP Ma ZG Wu BJ
author_facet	Zhang XW Chen GJ Zhang TP Ma ZG Wu BJ
author_sort	Zhang XW
title	Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation
title_short	Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation
title_full	Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation
title_fullStr	Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation
title_full_unstemmed	Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation
title_sort	effects of pegylated lipid nanoparticles on the oral absorption of one bcs ii drug: a mechanistic investigation
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/30780422131b439ca9eb1c8c87439ead
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_version_	1718401302163095552

Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

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