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

Authors Ait Bachir Z, Huang Y, He M, Huang L, Hou X, Chen R, Gao F

Received 6 March 2018

Accepted for publication 28 June 2018

Published 24 September 2018 Volume 2018:13 Pages 5657—5671

DOI https://doi.org/10.2147/IJN.S167443

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Thiruganesh Ramasamy

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


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

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