Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles

Zaina Ait Bachir,1,* YuKun Huang,1,* MuYe He,1 Lei Huang,1 XinYu Hou,1 RongJun Chen,2 Feng Gao1,3,4 1Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Department of Chemical Engineering, Imper...

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Autores principales:	Ait Bachir Z, Huang Y, He M, Huang L, Hou X, Chen R, Gao F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	chitosan pegylation nanoparticles methotrexate drug delivery systems Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/015fc1ff071945f2800143dff5927f03
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spelling	oai:doaj.org-article:015fc1ff071945f2800143dff5927f032021-12-02T07:25:56ZEffects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles1178-2013https://doaj.org/article/015fc1ff071945f2800143dff5927f032018-09-01T00:00:00Zhttps://www.dovepress.com/effects-of-peg-surface-density-and-chain-length-on-the-pharmacokinetic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zaina Ait Bachir,1,* YuKun Huang,1,* MuYe He,1 Lei Huang,1 XinYu Hou,1 RongJun Chen,2 Feng Gao1,3,4 1Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK; 3Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 4China Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: One of the most important aspects of drug delivery is extended nanoparticle (NP) residence time in vivo. Herein, we report a series of methotrexate (MTX)-loaded chitosan (CS) NPs coated with differently sized methoxy polyethylene glycol (mPEG) at different mPEG surface densities. Materials and methods: MTX was incorporated into NPs (112.8–171.2 nm in diameter) prepared from the resulting mPEG-g-CS. The NPs had a zeta potential of +7.4–35.0 mV and MTX loading efficiency of 17.1%–18.4%. MTX/mPEG-g-CS NPs showed an initial burst release of MTX followed by a sustained-release profile in PBS at pH 7.4. Results: The in vitro cellular uptake study showed that MTX accumulation in J774A.1 macrophage cells decreased with increasing the mPEG surface density or the mPEG molecular weight. The pharmacokinetic study on Sprague Dawley rats revealed an increase in AUC0–72 h (area under the plasma drug concentration–time curve over a period of 72 hours) with increasing the mPEG surface density or the mPEG molecular weight and a linear correlation between the mPEG surface density and AUC0–72 h. Conclusion: The biodistribution study on Institute of Cancer Research (ICR) mice revealed that MTX/mPEG-g-CS NPs significantly enhanced blood circulation time in the body and decreased accumulation in liver, spleen, and lung. These results suggest the potential of the mPEG-g-CS NPs as a promising candidate for drug delivery. Keywords: chitosan, PEGylation, nanoparticles, methotrexate, drug delivery systemsAit Bachir ZHuang YHe MHuang LHou XChen RGao FDove Medical Pressarticlechitosanpegylationnanoparticlesmethotrexatedrug delivery systemsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5657-5671 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	chitosan pegylation nanoparticles methotrexate drug delivery systems Medicine (General) R5-920
spellingShingle	chitosan pegylation nanoparticles methotrexate drug delivery systems Medicine (General) R5-920 Ait Bachir Z Huang Y He M Huang L Hou X Chen R Gao F Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
description	Zaina Ait Bachir,1,* YuKun Huang,1,* MuYe He,1 Lei Huang,1 XinYu Hou,1 RongJun Chen,2 Feng Gao1,3,4 1Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK; 3Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 4China Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: One of the most important aspects of drug delivery is extended nanoparticle (NP) residence time in vivo. Herein, we report a series of methotrexate (MTX)-loaded chitosan (CS) NPs coated with differently sized methoxy polyethylene glycol (mPEG) at different mPEG surface densities. Materials and methods: MTX was incorporated into NPs (112.8–171.2 nm in diameter) prepared from the resulting mPEG-g-CS. The NPs had a zeta potential of +7.4–35.0 mV and MTX loading efficiency of 17.1%–18.4%. MTX/mPEG-g-CS NPs showed an initial burst release of MTX followed by a sustained-release profile in PBS at pH 7.4. Results: The in vitro cellular uptake study showed that MTX accumulation in J774A.1 macrophage cells decreased with increasing the mPEG surface density or the mPEG molecular weight. The pharmacokinetic study on Sprague Dawley rats revealed an increase in AUC0–72 h (area under the plasma drug concentration–time curve over a period of 72 hours) with increasing the mPEG surface density or the mPEG molecular weight and a linear correlation between the mPEG surface density and AUC0–72 h. Conclusion: The biodistribution study on Institute of Cancer Research (ICR) mice revealed that MTX/mPEG-g-CS NPs significantly enhanced blood circulation time in the body and decreased accumulation in liver, spleen, and lung. These results suggest the potential of the mPEG-g-CS NPs as a promising candidate for drug delivery. Keywords: chitosan, PEGylation, nanoparticles, methotrexate, drug delivery systems
format	article
author	Ait Bachir Z Huang Y He M Huang L Hou X Chen R Gao F
author_facet	Ait Bachir Z Huang Y He M Huang L Hou X Chen R Gao F
author_sort	Ait Bachir Z
title	Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
title_short	Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
title_full	Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
title_fullStr	Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
title_full_unstemmed	Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
title_sort	effects of peg surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/015fc1ff071945f2800143dff5927f03
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Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles

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