姜黄素磷脂载体的表征及肠吸收研究

The Characteristics and in Situ Intestine Absorption of Curcumin Complex and Curcumin Liposomes Using Phospholipid as Vehicles

目的以磷脂为主要材料制备合适的载体,改善姜黄素的口服吸收。方法分别制备姜黄素磷脂复合物和脂质体,从包封率、形态、粒径、结构等方面进行表征,并通过大鼠在体肠吸收实验比较两者的肠吸收。结果姜黄素磷脂复合物和脂质体的包封率分别为(90.81±1.32)%和(81.59±2.41)%,粒径分别为(91.69±12.26)和(76.39±8.58)nm,Zeta电位分别为(-13.73±4.37)和(-11.27±1.26)。透射电镜和原子力显微镜观察到两种磷脂载体分散于水后均形成圆形或椭圆形的囊泡。DSC、IR和Roman光谱分析证实,磷脂复合物中姜黄素通过羟基与磷脂的P O基形成氢键结合,而脂质体中药物和磷脂间无化学键结合。磷脂复合物和脂质体的肠吸收膜表观渗透系数分别为(1.131 2±0.049 8)和(0.478 0±0.012 0)×10-6cm-2.s-1,较原料药分别提高了17.60和5.90倍。磷脂复合物在结肠、十二指肠和回肠的吸收显著高于脂质体。结论磷脂复合物较脂质体更能促进姜黄素的肠吸收。

OBJECTIVE To develop phospholipid vehicle to improve the bioavailability of curcumin after oral administration. METHODS Two phospholipid vehicles, including phospholipid complex and liposome, were prepared. The characteristics, such as entrapment efficiency, shape, size, and structure, were compared. An in situ recirculation method was used to investigate the intestinal absorption of both phospholipid vehicles. RESULTS Spherical or elliptical vesicles were observed under transmission electron micro- scope and atomic force microscope after the phospholipid vehicles were dispersed in water. The average entrapment efficieneies of phos- pholipid complex and liposome were （90. 81 ± 1. 32） % and （ 81.59 ±2.41 ） % respectively. The mean sizes and zeta electric potentials were （91.69 ± 12. 26） nm and （ - 13.73 ±4. 37） for the phospholipid complex, and （76. 39 ± 8.58） nm and （ - 11.27 ± 1.26） for the liposomes. DSC, IR and Raman spectrum verified that there was reaction between curcumin and the phospholipid polar group around phosphorus atom in the complex but not in the liposomes. The apparent permeability coefficients （Papv） in the whole in- testine were （1.131 2 ± 0. 049 8） and （0. 478 0 ± 0. 012 0）10-6 ^-2cm·S^-1 for the complex and liposome respectively, which were 17.60 times and 5.90 times higher than the crude drug. The absorption rate constants （Ka） and Papp of the complex were higher than the liposomes at duodenum, colon and ileum significantly. There was no difference at jejunum. CONCLUSION Phospholipid complex can promote the absorption of curcumin in a larger degree than liposomes.