PEG修饰青蒿素脂质纳米粒的体外释放及抗巨噬细胞摄取特性  

PEGylated Nanostructured Lipid Carriers Loaded with Artemisinin: in vitro Releasing Characteristics and Uptake by Mononuclear Phagocyte Macrophage

作　　者：栾淑伟[1] 赵青[1] 程慧芳[1] 王锐利[1] 梁桂贤[1] 张淑秋[1] 

机构地区：[1]山西医科大学药学院,太原030001

出　　处：《天然产物研究与开发》2015年第1期163-168,共6页Natural Product Research and Development

基　　金：国家自然基金项目(81373364)

摘　　要：研究聚乙二醇硬脂酸酯(PEGn-SA)修饰的青蒿素脂质纳米粒(PEGn-ART-NLC)体外释放及抗巨噬细胞(J774)摄取特性。采用高压乳匀法制备PEGn-SA(n=25、40、55)修饰的PEGn-ART-NLC及未修饰的青蒿素脂质纳米粒(ART-NLC),进行体外释放试验、抗吞噬实验、利用Gouy-Chapmann理论计算固定水化层厚度(FALT),并加以比较。在p H 7.4磷酸盐缓冲液(PBS)中,药物的体外释放度随PEGn-SA聚合度的改变而改变;加入血浆后,亦有改变。J774细胞对PEGn-ART-NLC的摄取量随PEGn-SA聚合度及J774细胞与制剂孵育时间的改变而改变;加入血浆孵育后,亦有改变。ART-NLC及三种PEGn-ART-NLC的固定水化层厚度分别为0.31、1.76、1.86和2.04 nm。结果表明该制剂体外具有良好的缓释特性及抗J774细胞吞噬性。Three long-circulating nanostructured lipid carriers loaded with artemisinin（ART） were prepared with polyethyleneglycol stearate of different polymerization degree（PEGn-SA,n = 25,40,55） by the high pressure homogenization method. The in vitro drug release,phagocytic uptake by J774 cells and fixed aqueous layer thickness（FALT） of nanostructured lipid carriers loaded with ART（ART-NLC） and three PEGylated nanostructured lipid carriers loaded with ART（PEGn-ART-NLC,n = 25,40,55） were examined and compared. The profiles of ART release from ART-NLC and PEGn-ART-NLC were studied at p H7. 4 with or without human plasma by high-performance liquid chromatography with post-column derivatization and UV detection. The ART release from PEGn-ART-NLC increased as the increasing of polymerization degree of polyethyleneglycol（PEG）. When plasma was added in release media,the ART in vitro releasing from NLCs was remarkably up-regulated. On the contrary,ART release was reduced as the increasing of polymerization degree of PEG. The ART in vitro phagocytic uptakes of PEGn-ART-NLCs by J774 cells were significantly lower than that of ART-NLC. ART phagocytic uptake by J774 cells increased as the increasing of polymerization degree of PEG or incubation time. Human plasma can noticeably up-regulate ART phagocytic uptake by J774 cells. The FALTs of ART-NLC and three PEGn-ART-NLC（n = 25,40,55） were 0. 31 nm,1. 76 nm,1. 86 nm and 2. 04 nm,respectively. These results suggested that the prepared artemisinin PEGylated nanostructured lipid carriers exhibited sustained release and antiphagocytic uptake characteristics.

关 键 词：青蒿素 脂质纳米粒 长循环 体外释放 吞噬细胞的摄取 

分 类 号：R944[医药卫生—药剂学]