Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles.
Effects of PEG surface density and chain length on the pharmacokinetics and biodistribution of methotrexate-loaded chitosan nanoparticles.
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DOI：
10.2147/ijn.s167443
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发表时间：
2018
影响因子：
8
通讯作者：
Gao F
中科院分区：
文献类型：
--
作者：
Ait Bachir Z;Huang Y;He M;Huang L;Hou X;Chen R;Gao F
延长纳米粒在体内的滞留时间是药物传递最重要的方面之一。在此，我们报道了一系列甲氨蝶呤(MTX)负载甲氨蝶呤(MTX)的壳聚糖(CS)纳米颗粒在不同表面密度下包覆不同尺寸的甲氧基聚乙二醇(Mpeg)。将甲氨蝶呤掺入到由得到的mpeg-CS制备的纳米颗粒(直径112.8-171.2 nm)中。纳米粒的Zeta电位为+7.4~35.0 mV，MTX的载药率为17.1%~18.4%。MTX/mGMP-g-CS纳米粒在pH为7.4时在PBS中有较好的缓释效果。体外细胞摄取研究表明，甲氨蝶呤在J774A.1巨噬细胞中的蓄积随着聚乙二醇膜表面密度或聚乙二醇单甲醚相对分子质量的增加而降低。在SD大鼠体内的药代动力学研究表明，随着聚乙二醇单甲醚表面密度或聚乙二醇单甲醚相对分子质量的增加，其AUC0-72 h(血药浓度-时间曲线下面积)增加，且与AUC0-72 h呈线性相关。肿瘤研究所(ICR)小鼠的生物分布研究表明，MTX/mpeg-CS纳米粒显著延长体内血液循环时间，减少在肝、脾和肺的蓄积。这些结果表明，mPEG-g-CS纳米粒有望成为药物输送的候选材料。
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 chito-san (CS) NPs coated with differently sized methoxy polyethylene glycol (mPEG) at different mPEG surface densities. 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. 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. 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.