摘要
目的优化和厚朴酚长循环脂质体(HLCL)制备工艺,并考察其体外释放及体内药动学特征。方法以和厚朴酚包封率为指标,通过正交试验优化HLCL组方,并对优化组方采用透射电子显微镜(TEM)扫描观察HLCL表面形态,透析法研究HLCL体外释放情况,UPLC-MS/MS法研究大鼠分别ig等剂量和厚朴酚及HLCL(20 mg/kg和厚朴酚)后的血浆药动学参数。结果 HLCL的最优制备条件为大豆磷脂酰胆碱-胆固醇-m PEG2000-DSPE的质量比为8∶1∶1、药脂质量比为1∶10、超声时间为12 min。在此条件下,HLCL在TEM下为圆球,包封率84.7%、载药量10.4%、平均粒径121.5 nm、Zeta电位-30.8 mV。HLCL体外释放缓慢,24 h在p H 1.2和p H 6.9释放介质中的累积释放率分别为80%和71%。大鼠ig给药后,HLCL组和厚朴酚的C_(max)、t_(max)、t_(1/2)分别为(23.29±11.76)ng/m L、(0.13±0.05)h和(10.59±5.72)h,和厚朴酚组的Cmax、tmax、t1/2分别为(79.34±56.32)ng/m L、(0.30±0.07)h和(4.44±3.14)h,两组的AUC0-∞无显著差异。结论与游离和厚朴酚相比,HLCL体外释放缓慢,体内吸收迅速、消除缓慢。
Objective To optimize the preparation process of honokiol long-circulating liposomes（HLCL） and study the in vitro and invivo release. Methods An orthogonal experiment was designed to optimize the composition of HLCL using entrapment efficiency as evaluation indicator. The liposome surface morphology was observed by transmission electron microscope（TEM）, and the liposome release in vitro was studied by dialysis method. The concentration of honokiol in rat plasma was determined by the established LC-MS/MS method, and the differences in pharmacokinetic parameters were compared after honokiol and HLCL（20 mg/kg） were orally administered to SD male rats, respectively. Results The optimal composition of HLCL was 8∶1∶1 for soya phosphatidyl choline-cholesterol-m PEG2000-DSPE, and 1∶10 for honokiol-liposome materials with the ultrasonic time of 12 min. Under the optimized conditions, HLCL was sphere with mean particle size of 121.5 nm and mean Zeta potential of-30.8 m V, the encapsulation efficiency and drug-loading content was 84.7% and 10.4%, respectively. In vitro release results showed that the liposomes could be gently and slowly release with the 24 h cumulative release rate at p H 1.2 and p H 6.9 dissolve medium of 80% and 71%, respectively. Based on the pharmacokinetic results, Cmax, tmax, and t1/2 were（23.29 ± 11.76） ng/m L,（0.13 ± 0.05） h and（10.59 ± 5.72） h for HLCL, and（79.34 ± 56.32） ng/m L,（0.30 ± 0.07） h and（4.44 ± 3.14） h for honokiol, respectively. There was no significant difference about the AUC0-∞ following oral administration of honokiol and HLCL at isodose honokiol（20 mg/kg）. Conclusion Compared with honokiol, HLCL was released gently and slowly in vitro, absorpted rapidly and eliminated slowly in vivo.
出处
《中草药》
CAS
CSCD
北大核心
2017年第18期3720-3727,共8页
Chinese Traditional and Herbal Drugs
基金
湖北省技术创新专项重大项目(2016ACA140)
