基于甘草酸为载体的紫杉醇-甘草酸纳米胶束的构建和口服生物利用度的评价

目的：构建紫杉醇-甘草酸纳米胶束（paclitaxel-loaded glycyrrhizic acid micelles）并对其理化性质及口服生物利用度进行考察。方法：所制备纳米胶束的包封率和载药量通过高效液相色谱法检测并计算；采用动态光散射仪测定其粒径分布；以紫杉醇溶液作为对照组，考察纳米胶束口服给药后药动学的变化；采用在体in-situ肠封闭法考察不同肠道对紫杉醇的吸收差异。结果：采用超声分散法制备载紫杉醇-甘草酸纳米胶束大小均匀，平均粒径为（245.42±5.62） nm；药物胶束的包封率为90.22%±0.27% （n=3），载药量为7.90%±0.10%（n=3）；与对照组相比，纳米胶束口服生物利用度提高约6倍，很大程度上是由于紫杉醇在空肠以及结肠上吸收的增加引起。结论：该方法所制备的纳米胶束制剂能有效提高紫杉醇口服生物利用度，发挥甘草酸药物载体的特点以及药用安全性的优点，该纳米胶束可作为紫杉醇新的药物传递系统，具有临床应用前景。

Preparation and oral bioavailability of paclitaxel loaded glycyrrhizic acid nano-micelles using glycyrrhizic acid as the drug carrier

OBJECTIVE To study the preparation and oral bioavailability of paclitaxel (PTX) loaded glycyrrhizic acid (GA) nano-micelles (paclitaxel loaded glycyrrhizic acid micelles).METHODS The entrapment rate and drug loading rate were determined by high performance liquid chromatography (HPLC).The dynamic light scattering was exploited to determine the particle size and the distribution of the micelles.The pharmacokinetic study via oral administration of PTX-loaded GA micelles and PTX solution were carried out.The intestinal absorption of PTX from the PTX solution and PTX-loaded GA micelle solution were studied by in situ closed loop method.RESULTS The micelles had a mean diameter of (245.42±5.62) nm prepared by the ultrasonic dispersion method.The entrapment rate was 90.22%±0.27% and the drug loading of the micelles was 7.90%±0.10% (n=3).Compared with PTX solution,the PTX-loaded GA micelles led to a 6-fold enhancement in the oral bioavailability of PTX,which could be largely due to the increased absorption in jejunum and colon intestine.CONCLUSION As a result of the effect as the drug carrier and the security of GA,PTX-loaded GA micelles would be a new drug delivery system for PTX and a promising preparation in clinic for the treatment of tumors.