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目的制备染料木素(GEN)MePEG-PLGA共聚物胶束,考察其理化性质、初步稳定性及静脉给药后大鼠体内的药动学行为。方法采用改良的自乳化溶剂挥发法制备胶束,考察其形态、包封率、载药量、粒径和Zeta电位;采用动态膜透析技术考察其释药行为,并对其释药规律进行拟合;将胶束冻干品置于4℃冰箱中保存,分别于放置1 d、10 d、1个月、3个月、6个月后取样,考察其包封率和载药量变化;对健康大鼠尾静脉注射GEN胶束,采用HPLC测定GEN在大鼠体内的血药浓度,采用DAS 2.0软件处理血药浓度数据,SPSS 17.0软件对主要药动学参数进行统计学分析。结果制备所得胶束的包封率为(84.43±2.93)%,载药量为(2.63±0.91)%,粒径为(63.75±4.12)nm;GEN胶束的释药行为最符合Weibull模型;GEN胶束冻干品6个月渗漏率为2.45%,载药量下降0.18%;大鼠尾静脉注射GEN胶束和GEN乳剂40 mg.kg 1后,主要药动学参数AUC0-t分别为(99.46±4.77)mg.L 1.h和(57.51±1.37)mg.L 1.h,t1/2分别为(7.48±1.15)h和(4.95±1.15)h,Cmax分别为(16.03±1.20)mg.L 1和(16.73±1.10)mg.L 1,CL分别为(0.36±0.02)L.h 1.kg 1和(0.67±0.02)L.h 1.kg 1。结论制备所得的GEN胶束形态规整,粒径分布狭窄,包封率较高,具有一定的缓释特征,稳定性良好,并且明显改变了GEN的药动学行为,使其消除减慢,同时提高了药物的生物利用度。
OBJECTIVE To prepare the micelles of genistein (MePEG-PLGA) and investigate its physicochemical properties, initial stability and pharmacokinetics in rats after intravenous administration. Methods The micelles were prepared by a modified self-emulsifying solvent evaporation method. The morphology, entrapment efficiency, drug loading, particle size and Zeta potential were investigated. The release behavior of the micelles was investigated by dynamic membrane dialysis. The micellar lyophilized samples were stored in refrigerator at 4 ℃, respectively. Samples were taken after 1 d, 10 d, 1 month, 3 months and 6 months respectively to investigate the encapsulation efficiency and drug loading. GEN micelles were injected into the caudal vein of healthy rats. The plasma concentrations of GEN in rats were determined by HPLC. DAS 2.0 software was used to process plasma concentration data. The main pharmacokinetic parameters were analyzed by SPSS 17.0 software. Results The encapsulation efficiency was (84.43 ± 2.93)% and the drug loading was (2.63 ± 0.91)% and the size was (63.75 ± 4.12) nm. The release behavior of GEN micelles was the most suitable for Weibull model. GEN emulsion micelles freeze-dried 6 months the rate of 2.45%, drug loading decreased 0.18%; the tail vein injection of GEN micelles and GEN emulsion 40 mg.kg 1, the main pharmacokinetic parameters AUC0-t, respectively (99.46 ± 4.77) mg.L 1.h and (57.51 ± 1.37) mg.L 1.h respectively, and the values of t1 / 2 were (7.48 ± 1.15) h and (4.95 ± 1.15) h, respectively 1.20) mg.L 1 and (16.73 ± 1.10) mg.L 1 respectively, with CL values of (0.36 ± 0.02) Lh 1.kg 1 and (0.67 ± 0.02) Lh 1.kg 1, respectively. Conclusions GEN micelles obtained by the preparation have regular shape, narrow particle size distribution, high entrapment efficiency, certain sustained release characteristics and good stability, and significantly change the pharmacokinetic behavior of GEN to slow down its elimination. At the same time Improve the bioavailability of the drug.