文献类型：期刊文献

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

作者：Bachir, Zaina Ait[1];Huang, YuKun[1];He, MuYe[1];Huang, Lei[1];Hou, XinYu[1];Chen, RongJun[2];Gao, Feng[1,3,4]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai, Peoples R China;[2]Imperial Coll London, Dept Chem Engn, South Kensington Campus, London SW7 2AZ, England;[3]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Meilong Rd, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, China Shanghai Key Lab New Drug Design, Shanghai, Peoples R China

年份：2018

卷号：13

起止页码：5657

外文期刊名：INTERNATIONAL JOURNAL OF NANOMEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000445525100002)】；

基金：This work was supported by Shanghai Municipal Natural Science Foundation (contract no 17ZR1406600), Science and Technology Commission of Shanghai Municipality (contract no 10DZ2220500), and The Shanghai Committee of Science and Technology (grant no 11DZ2260600).

语种：英文

外文关键词：chitosan; PEGylation; nanoparticles; methotrexate; drug delivery systems

摘要：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 AUC(0-72) 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 AUC(0-72) 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.