口服芹菜素固体脂质纳米粒制剂学及药动学研究

Studies on Pharmacy Characters and Pharmacokinetics of Oral Apigenin Loaded Solid Lipid Nanoparticle

目的本研究对所制得的芹菜素固体脂质纳米粒的制剂学性质和药动学进行研究。方法使用激光粒度仪,Zeta电位值测定仪,透射电镜,X-射线衍射,体外溶出实验考察芹菜素固体脂质纳米粒的制剂学性质;以自制芹菜素混悬液为对照组,考察了大鼠口服芹菜素固体脂质纳米粒的药动学过程。结果透射电镜观察纳米粒的形态发现该纳米粒为类球形粒子;平均粒径为135nm;Zeta电位为-18.90mV;测定药物在释放介质中的释放符合一级释放方程。X-射线衍射证明,芹菜素在固体脂质纳米粒中以无定形形式存在。口服药动学结果表明,芹菜素固体脂质纳米粒组的平均AUC0-t为17.337mg·h·L-1,而对照组为5.3mg·h·L-1。纳米粒组的ρmax为3.07mg·L-1,明显高于对照组的1.544mg·L-1。纳米粒组的消除速率常数Ke较低,为0.232h-1,低于对照组。结论芹菜素固体脂质纳米粒的相对生物利用度为327%。芹菜素固体脂质纳米粒可有效提高芹菜素的生物利用度。

OBJECTIVE To investigate the pharmacy characters and pharmacokinetic processes of the prepared apigenin loaded solid lipid nanoparticles （AP-SLN）. METHODS The pharmacy characters of AP-SLN were investigated with the mean size, ζ potential, transmission electron microscopy, and in vitro drug release. The pharmacokinefic processes of oral AP-SLN of the rats were also studied, while apigenin suspension was used as control group. RESULTS The appearance of AP-SLN was examined by transmission electron microscopy as sphere-like with the mean size of 135 nm, the potential of-18.90 mV, respectively. The in vitro release profiles were expressed by first-order release equation. Using X-ray, it was comfirmed that apigenin was encapsulated in solid lipid nanoparticles as amorphous. The average AUC0-t of SLN group was 17.337 mg·h·L^-1, while the AUC0-t of control group was 5.3 mg·h·L^-1. The ρmax of SLN group was 3.07 mg·L^-1, obviously higher than 1.544 mg·L^-1 of control group. The elimination rate constant, Ke, of SLN group was 0.232 h^-1, lower than that of the control group. The relative bioavailability of the AP-SLN was 327%. CONCLUSION The results of oral administration pharmacokinetics indicated that SLN significantly enhanced the oral bioavailability of AP.