叶酸靶向乙酰普鲁兰纳米粒的制备及其靶向作用  

Preparation of Folate Targeted Pullulan Acetate Nanoparticles and Cell Uptake in vitro

作　　者：张慧珠[1,2] 张其清[2] 

机构地区：[1]华北煤炭医学院药理教研室,唐山063000 [2]中国医学科学院/北京协和医学院生物医学工程研究所,天津300192

出　　处：《高等学校化学学报》2009年第6期1146-1151,共6页Chemical Journal of Chinese Universities

基　　金：国家"九七三"计划(批准号:2006CB933300)资助

摘　　要：以普鲁兰多糖为主链,通过乙酰化反应合成了疏水性的乙酰普鲁兰(PA),然后以N,N′-二环己基碳二亚胺(DCC)为偶联剂,4-二甲氨基吡啶(DMAP)为催化剂,将叶酸与PA偶联(FPA);采用1HNMR和X射线晶体衍射(XRD)等方法对产物结构进行了表征.采用溶剂扩散法制备包载表阿霉素的PA和FPA纳米粒,载药纳米粒形态为球形,动态光散射粒径分析显示载药纳米粒粒径随载药量增加而增大.透析法测定纳米粒中表阿霉素的体外释放表明,FPA纳米粒中药物释放速度快于PA纳米粒;采用激光共聚焦显微镜观察PA/EPI及FPA/EPI纳米粒在KB细胞的摄取情况,结果表明,FPA/EPI纳米粒进入细胞主要通过叶酸受体途径,而PA/EPI纳米粒进入细胞与叶酸受体无关,提示FPA将成为具有一定肿瘤靶向作用的新型载体.Pullulan acetate （PA） was synthesized via the reaction of pullulan with acetic anhydride. Folate was coupled to PA by N, N＇-dicyclohexylcarbodiimide （ DCC ） and 4-dimethylamino-pyridine （DMAP） mediated ester formation. The products were characterized with 1H NMR spectroscopy and X-ray diffraction （XRD）. The solvent diffusion method was used to prepare epirubicin （EPI） loaded nanoparticles. The morphology of nanoparticles was sphere measured by transmission electron microscopy（TEM）, and the size of nanoparticles was 200-500 nm determined by dynamic light scattering（DLS）. The results revealed that drug loading efficiencies and diameters of nanoparticles increased as the drug/materials ratio increasing. The EPI release rate in vitro was measured using a dialysis tube. Cellular uptake extents of PA and FPA were evaluated with confocal microscopy. The result show more fluorescently labeled cells can be clearly visualized in the absence of folate in the medium than presence of 1 mmol/L folate when KB cell incubated with FPA/EPI nanoparticles, suggesting FPA/EPI nanoparticles are endocytosed in a folate receptor-mediated manner.

关 键 词：叶酸受体 肿瘤靶向 乙酰普鲁兰 纳米粒 溶剂扩散法 

分 类 号：O62[理学—有机化学] O636.1[理学—化学]