姜黄素长循环脂质体的制备及药动学研究  

Preparation of curcumin-loaded long-circulating liposomes and its pharmacokinetics in rats

作　　者：尤佳[1] 戴东波[1] 何雯洁[1] 李刚[1] 宋述程 魏颖慧[1] 李范珠[1] 徐秀玲[1] 

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]杭州桐君堂中医门诊部,浙江杭州310007

出　　处：《中国中药杂志》2014年第7期1238-1242,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81274089);浙江省自然科学基金项目(LY12H28004)

摘　　要：姜黄素具有抗炎、抗氧化、降血脂和抗肿瘤等多重药理作用,但其水溶性差、体内消除快,半衰期短的缺陷使其临床应用受到限制。将姜黄素制备成长循环脂质体(Cur-LCL)可望改善其水溶性差的问题并有效延长其体内循环时间。该研究以乙醇注入法制备Cur-LCL,考察其理化性质,并以姜黄素原料药(Cur)和姜黄素普通脂质体(Cur-Lips)为对照组,通过体外释放和大鼠尾静脉注射给药后药动学行为考察Cur-LCL的长循环作用。结果表明所制备的Cur-LCL呈类圆形,粒径分布均匀,平均粒径110 nm,Zeta电位-5.8 mV,包封率和载药量分别为80.25%,2.06%;体外释放结果显示Cur-LCL在7,24 h内累积释放率分别达到48.95%,88.92%,与Cur和Cur-Lips相比具有明显缓释特征;大鼠尾静脉注射给药后的药动学研究表明,与Cur和Cur-Lips相比,Cur-LCL的AUC显著增大(P<0.01),CL显著降低(P<0.01),且t1/2β延长至2.45 h,分别是Cur的13倍(P<0.01)和Cur-Lips的1.8倍(P<0.01)。结果表明,Cur-LCL体内代谢消除显著减缓,具有长循环的作用。Curcumin has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin are major challenge in its development as a useful drug. To overcome many of these problems, curcumin-loaded long-circulating liposomes （Cur-LCL） were prepared by the ethanol injection method. Morphology of Cur-LCL was observed by transmission electron microscope, mean particle size and Zeta potential were detected by laser particle size analyzer, entrapment efficiency and drug loading were evaluated by ultracentrifugation. The drug release behavior in vitro and pharmacokinetic behavior in rats of Cur-LCL were investigated with curcumin（Cur）and curcumin liposomes （Cur-Lips） as control. The results showed that the mean diameter of Cur-LCL was 110 nm, the Zeta potential was -5.8 mV. The entrapment efficiency and drug loading of Cur-LCL was 80.25%, 2.06%, respectively. The release behavior in vitro studied by dialysis in PBS buffer showed significant sustained release profile that 48.95% Cur were released from Cur-LCL in 7 h, 88.92% in 24 h. The pharmacokinetic parameters showed that compared with Cur and Cur-Lips, the t1/2β of Cur-LCL was extended to 13 and 1.8-fold, respectively. Besides, the AUC values was significantly increased（P〈0.01）, and the clearance was evidently decreased（P〈0.01）. These results from in vitro and in vivo indicated that Cur-LCL were able to realize controlled drug release and increase circulation time.

关 键 词：姜黄素 长循环脂质体 体外释放 药动学 

分 类 号：R285[医药卫生—中药学]