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聚乙二醇化脂质双层包被介孔硅纳米粒子用于紫杉醇和姜黄素的共递送:设计、表征及其细胞毒性作用。

PEGylated Lipid bilayer coated mesoporous silica nanoparticles for co-delivery of paclitaxel and curcumin: Design, characterization and its cytotoxic effect.

机构信息

The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.

Department of Materials Science & Engineering, Tsinghua University, Beijing 100084, PR China.

出版信息

Int J Pharm. 2018 Jan 30;536(1):272-282. doi: 10.1016/j.ijpharm.2017.10.043. Epub 2017 Oct 24.

DOI:10.1016/j.ijpharm.2017.10.043
PMID:29079221
Abstract

Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754nm and particle size of 115±15nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10-15nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50mg MSNs, ratio of MSNs to lipid (w/w)=1:1.11, and ratio of lipid to CHO (w/w)=3.93:1. The average experimental EE, EE and stability score value were (77.48±2.73) %, (30.70±3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect.

摘要

采用刻蚀法制备了孔径为 2.754nm、粒径为 115±15nm 的有序介孔硅纳米粒子(MSNs)。采用薄膜水化法在 MSNs 表面包覆均匀的 10-15nm 厚的聚乙二醇化脂质双层。采用单因素试验和 Box-Behnken 设计对紫杉醇(Tax)和姜黄素(Cur)共包封到聚乙二醇化脂质双层包覆介孔硅纳米粒子(PLMSNs)的过程进行了系统优化和表征。通过反相高效液相色谱(RP-HPLC)法测定包封药物的浓度。优化的因素设置如下:50mg MSNs、MSNs 与脂质(w/w)的比例=1:1.11、脂质与 CHO(w/w)的比例=3.93:1。根据上述条件,平均实验 EE、EE 和稳定性评分值分别为(77.48±2.73)%、(30.70±3.56)%和 4 分。Tax-Cur-PLMSNs 的形态学测定表明,复合纳米粒子为具有均匀分散性的球形颗粒。体外释放实验表明,与 Tax 粉末混悬液相比,PLMSNs 提高了 Tax 的溶解度,并表现出持续释放的特性。Tax-Cur-PLMSNs 对犬乳腺癌细胞表现出明确且持续的促细胞毒性作用。Tax-Cur-PLMSNs 的这种延长和增强的活性可能归因于其持续释放的效果。

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