目的 制备红花黄色素（safflower yellow pigment，SY）纳米柔性脂质体（nano-flexible liposome，NFL）（SY-NFL）以提高SY的黏膜透过率，并考察SY-NFL的药剂学相关性质。方法 采用薄膜分散法制备SY-NFL，以包封率和载药量为指标，通过单因素试验及Box-Behken设计-响应面法（Box-Behken design-response surface method，BBD-RSM）优化SY-NFL最佳处方，再以包封率、粒径及多分散指数（polydispersity index，PDI）值优化其成型工艺；对SY-NFL进行结构、ζ电位、粒径等药剂学性质进行考察；采用水平扩散池法考察SY-NFL对SY黏膜透过率的影响。结果 当脂药比65.68∶1、脂胆比31.88∶1、丙二醇质量分数15%，经探头超声转速8 000 r/min、超声5 min，可制备包封率为（81.440±4.250）%、载药量为（1.510±1.450）%，粒径为（534.500±1.960）nm，PDI为0.110±0.010的SY-NFL。不同温度放置4周后，SY-NFL渗漏率始终低于SY的普通脂质体（common liposome，SY-CL），SY-NFL变形性也高于SY-CL；SY-NFL的累积透过量始终高于SY-CL和SY原料药，4 h时，SY-NFL中羟基红花黄色素A（hydroxysafflor yellow A，HSYA）的累积透过率分别为SY-CL和SY原料药的1.38倍和1.65倍。结论 采用薄膜分散法可制备性能良好的SY-NFL，其具有较高的包封率、变形性及稳定性，可作为递送SY透黏膜吸收的纳米载体。

Objective Safflower yellow pigment (SY) nano-flexible liposome (NFL) (SY-NFL) was prepared to improve the mucosal permeability of SY, and the pharmaceutical properties of SY-NFL were investigated. Methods SY-NFL was prepared by thin film dispersion method. Single factor test and Box-Behken design-response surface method were used to optimize the optimum formulation of SY-NFL, and then the forming process was optimized according to the encapsulation rate, particle size and PDI. The structure, potential and particle size of SY-NFL were investigated. The effect of SY-NFL on the mucosa permeability of SY was investigated by horizontal diffusion cell. Results When the ratio of lipid to drug was 65.68:1, the ratio of lipid to cholesterol was 31.88:1, the mass fraction of propylene glycol was 15%, and the ultrasonic speed of the probe was 8 000 r/min and the ultrasonic speed was 5 min, the encapsulation rate of SY-NFL was (81.440 ±4.250)%, the drug loading was (1.510 ±1.450)%, and the particle size was (534.500 ±1.960) nm. The PDI was 0.110 ±0.010. After four weeks at different temperatures, the leakage rate of SY-NFL was always lower than that of SY’s ordinary liposomes (SY-CL), and the deformation of SY-NFL was also higher than that of SY-CL. The cumulative permeability of SY-NFL was always higher than that of SY-CL and SY. At 4 h, the cumulative through rate of hydroxyl safflower yellow A (HSYA) in SY-NFL was 1.38 times and 1.65 times of that of SY-CL and SY, respectively. Conclusion SY-NFL can be prepared by thin film dispersion method, which has high encapsulation rate, deformation and stability, and can be used as a nanometer carrier to deliver SY through mucosal absorption.

R283.6

山西省卫生健康委科研课题:红花黄色素纳米柔性脂质体的制备及评价(2022146);山西省卫生健康委员会重点实验室建设:山西省"四个一批"科技兴医创新计划项目"中药新产品关键技术开发省级重点培育实验室项目"(2020SYS09);山西省技术创新中心项目:中药制剂研发省技术创新中心(202104010911024);山西省科技创新人才团队专项:中药制剂研发(202204051002028)