甘草次酸衍生物受体靶向复方脂质体的制备及其体外释放研究

目的：合成两亲性导向分子甘草次酸衍生物3-琥珀酸-30-硬脂醇甘草次酸酯（18-GA-Suc），研究其掺入甘草次酸-丹参酮ⅡA-丹酚酸B复方脂质体（GTS-Lip）的制备工艺，并考察其体外释放规律。方法：采用1HNMR和13CNMR表征18-GA-Suc的结构，通过单因素考察确定18-GA-Suc的投料量，低速离心法测定其掺入比率，比较修饰前后复方脂质体的理化性质，以平衡透析法考察甘草次酸衍生物受体靶向的甘草次酸-丹参酮ⅡA-丹酚酸B复方脂质体（Suc-GTS-Lip）中3种成分的体外释放规律。结果：优化的处方工艺为：18-GA-Suc投料量为膜材的10%（mol·mol-1），掺入比率为96.58%。Suc-GTS-Lip形态圆整，分布均匀，其中甘草次酸（GA）、丹参酮ⅡA（TSN）和丹酚酸B（SalB）的平均包封率分别为86.15%，81.70%，91.05%，平均粒径为128.7 nm，平均Zeta电位为-15.5mV。GA和TSN体外释放规律符合Higuchi方程，SalB体外释放规律符合Hixon-crowell方程。结论：甘草次酸衍生物（18-GA-Suc）能在脂质体膜上成功表达，本脂质体制备工艺稳定，GA、TSN和SalB 3种成分在体外均具有一定的缓释作用，为进一步研究其肝靶向性奠定了基础。

Preparation and in Vitro Release of Glycyrrhetinic Acid-tanshinone IIA-salvianolic acid B Compound Liposomes with Glycyrrhetinic Acid Derivative as Targeting Molecule

This article was aimed to study the preparation process of glycyrrhetinic acid (GA)-tanshinone IIA (TSN)-salvianolic acid B (SalB) compound liposomes with 3-succinic-30-stearyl glycyrrhetinic acid (18-GA-Suc) which is one of amphiphilicglycyrrhetinic acid derivatives as targeting molecule. The structure of the targeting molecule was validated by 1H-NMR and 13C-NMR methods. The feed ratio of 18-GA-Suc was optimized through single factor test and the incorporation ratio of 18-GA-Suc was determined by low-speed centrifugation. Meanwhile, physicochemical properties between Suc-GTS-Lip and GTS-Lip were compared. In vitro release studies of three components in Suc-GTS-Lip were conducted by equilibrium dialysis method. The results showed that the optimum conditions were when the feed ratio of 18-GA-Suc was 10% lipid liposomal membrane (mol·mol-1). It revealed that the incorporation ratio of 18-GA-Suc was 96.58%, and the encapsulation efficiencies of GA, TSN, and SalB were about 86.15%, 81.70%, and 91.05%, respectively. In addition, the Suc-GTS-Lip was spherical and uniformly dispersed with particle size of 128.7 nm and zeta potential of -15.5 mV. The release model of GA and TSN was fitted well with Higuchi equation, while SalB was fitted well with Hixon-crowell equation. It was concluded that Glycyrrhetinic acid derivatives (18-GA-Suc) can be successfully expressed in the liposome membrane, and the optimal preparation method of Suc-GTS-Lip was stable. All three components encapsulated into liposomes had sustained-release effects, which laid a good foundation for its further study about liver-targeting.