延胡索乙素聚乳酸纳米粒的制备及其体内药动学研究

目的制备延胡索乙素聚乳酸纳米粒,并考察其体内药动学。方法改良的自乳化溶剂挥发法制备聚乳酸纳米粒,测定平均粒径、Zeta电位、包封率、载药量、体外释药,透射电镜观察形态。大鼠随机分为2组,分别灌胃给予延胡索乙素及其聚乳酸纳米粒0??5%CMC?Na混悬液(20 mg/kg),于0、0.25、0.5、1、2.0、2.5、3、4、6、8、10、12 h采血,HPLC法测定延胡索乙素血药浓度,计算主要药动学参数。结果所得纳米粒呈球形,平均粒径为(176.18±5.21)nm,Zeta电位为(-11.1±1.5)mV,包封率为(76.64±0.23)%,载药量为(5.01±0.12)%,36 h内累积释放度低于30%,释药过程符合Weibull模型(r=0.9884)。与原料药比较,聚乳酸纳米粒t_max、t_1/2延长(P<0.05,P<0.01),C_max、AUC_0-t、AUC_0-∞升高(P<0.01),相对生物利用度增加至2.41倍。结论聚乳酸纳米粒可促进延胡索乙素体内吸收,改善其口服生物利用度。

Preparation and in vivo pharmacokinetics of tetrahydropalmatine polylactic acid nanoparticles

AIM To prepare tetrahydropalmatine polylactic acid nanoparticles and to investigate their in vivo pharmacokinetics.METHODS Polylactic acid nanoparticles were prepared by modified self?emulsifying solvent evaporation method,after which average particle size,Zeta potential,encapsulation efficiency,drug loading and in vitro drug release were determined,and the morphology was observed by transmission electron microscopy.Rats were randomly assigned into two groups and given intragastric administeration of the 0.5%CMC?Na suspensions of tetrahydropalmatine polylactic acid and its nanoparticles(20 mg/kg),respectively,after which blood collection was performed at 0,0.25,0.5,1,2.0,2.5,3,4,6,8,10,12 h.HPLC was adopted in the plasma concentration determination of tetrahydropalmatine polylactic acid,and the main pharmacokinetic parameters were calculated.RESULTS The obtained spherical nanoparticles demonstrated the average particle size of(176.18±5.21)nm,Zeta potential of(-11.1±1.5)mV,encapsulation efficiency of(76.64±0.23)%,drug loading of(5.01±0.12)%,and accumulative release rate of less than 30%within 36 h,the drug release accorded with Weibull model(r=0.9884).Compared with raw medicine,the polylactic acid nanoparticles demonstrated prolonged t_max and t_1/2(P<0.05,P<0.01),and increased Cmax,AUC_0-t and AUC_0-∞(P<0.01),whose relative bioavailability was enhanced to 2.41 times.CONCLUSION Polylactic acid nanoparticles can promote the in vivo absorption of tetrahydropalmatine and improve its oral bioavailability.