温敏性甘草次酸/壳聚糖药物载体的制备及其胶束的性能研究  

Preparation of temperature-sensitive glycyrrhetinic acid-chitosan drug carrier and study on its micellar properties

作　　者：马亚萍[1,2] 黄一平[2] 赵呈雷[2] 王丽[1,2] 徐佳[1,2] 

机构地区：[1]南京中医药大学附属中西医结合医院,南京210046 [2]中国中医科学院江苏分院暨江苏省中医药研究院,南京210028

出　　处：《中国新药杂志》2015年第23期2733-2739,共7页Chinese Journal of New Drugs

基　　金：江苏省中医药局课题(LZ10368)

摘　　要：目的:制备同时具有温度敏感性和肝靶向性的药物载体N-异丙基丙烯酰胺-(甘草次酸-壳聚糖),将这种载体制备成为聚合物胶束,对该胶束的性质进行研究。方法:以壳聚糖为反应底物,通过两步N-酰化反应制备载体,用红外光谱仪和核磁共振氢谱仪鉴定产物结构。再用直接溶解超声法制备聚合物胶束溶液,测定胶束在不同温度下的粒径,观察胶束形态。结果:在反应物的比例为1∶2,时间为72 h时,N-异丙基丙烯酰胺-(甘草次酸-壳聚糖)氨基取代度可达30%以上。其聚合物胶束溶液具有一定的温度敏感性:在环境温度为25℃时平均粒径为154 nm,且随着温度的升高,粒径呈现出一定规律的变化,用透射电镜观察其形态呈球形。结论:所制备的N-异丙基丙烯酰胺-(甘草次酸-壳聚糖)聚合物胶束具有良好的理化性质和温度敏感性,为其作为药物载体提供了可能性,具有一定的发展前景。Objective： To synthesize a drug carrier that has not only temperature sensitivity but also liver targeting effect,turn the carrier into olymer micelles and then study the properties of the micelles. Methods： With chitosan as the reaction substrate,the carrier was synthesized by a two-step N-acylation reaction. Infrared spectrometer and nuclear magnetic resonance spectrometer were used for the identification of the structure of reaction product. Polymer micelle solution was prepared by direct dissolution and then ultrasonic treatmen. The average particle sizes of the micelles at different temperatures were determined. The morphology of the micelles was observed. Results： The amino substitution degree of N-isopropyl acrylamide-（ glycyrrhetinic acid-chitosan） reached above 30%when the ratio of reactants was 1∶ 2 and the reaction time was 72 h. The average particle size of the micelles was154 nm when the environmental temperature was 25 ℃,and with the increase of temperature,the particle size changed in a certain trend. The micelles were spherical when observed under transmission electron microscope.Conclusion： The prepared N-isopropyl acrylamide-（ glycyrrhetinic acid-chitosan） polymer micelles have desirable physical and chemical properties and temperature-sensitive properties,which provides basis for its use as a drug carrier,thus have a certain development prospect.

关 键 词：温敏性 肝靶向性 药物载体 胶束 

分 类 号：R943.42[医药卫生—药剂学]