木犀草素纳米结构脂质载体及其冻干粉的制备和体外释药研究

目的：制备木犀草素纳米结构脂质载体及其冻干粉，考察体外释放情况，并对其释药模型进行拟合。方法：热熔乳化超声法制备木犀草素纳米结构脂质载体，逐步考察药脂比、固液脂质比例、大豆磷脂和泊洛沙姆188比和表面活性剂总浓度等对包封率、载药量、粒径及Zeta电位的影响，采用正交试验得出木犀草素纳米结构脂质载体最佳处方，进一步制备成冻干粉并对体外释药模型进行拟合。扫描电镜观察纳米粒子形态，X射线粉末衍射法（XRPD）分析存在状态。结果：正交优化木犀草素纳米结构脂质载体的最佳处方的包封率为（77.62±1.51）%，载药量为（3.41±0.11）%，平均粒径为（167.91±6.44）nm，Zeta电位为（-27.7±2.6）mV，外观呈球形或椭圆形。木犀草素相纳米结构脂质载体冻干粉体外释药模型符合Weibull模型：lnln （1/1-M_t/M_∞）=1.025 1lnt-4.600 4（r=0.987 5）。木犀草素以无定型状态包封于纳米结构脂质载体中。结论：木犀草素纳米结构脂质载体工艺重复性良好，值得进一步研究。

Preparation of luteolin-nanostructured lipid carriers and freeze-dried powder and the study of drug release in vitro

OBJECTIVE To prepare luteolin nanostructured lipid carrier and its lyophilized powder, investigate the in vitro release, and fit its drug release model.METHODS Luteolin nanostructured lipid carriers were prepared by hot melt emulsification phacoemulsification. The effects of drug-lipid ratio, solid-liquid lipid ratio, soybean phospholipid and Poloxamer 188 ratio and total surfactant concentration on entrapment efficiency, drug loading, particle size and zeta potential were gradually investigated. The optimal formulation of luteolin nanostructured lipid carriers was obtained by orthogonal test. The lyophilized powder was further prepared and the in vitro drug release model was fitted. The morphology of nanoparticles was observed by scanning electron microscopy, and the presence state was analyzed by X-ray powder diffraction (XRPD).RESULTS The encapsulation efficiency, drug loading, particle size and the Zeta potential of the optimal formulation of lutelin-nanostructured lipid carriers were (77.62±1.51)%, (3.41±0.11)%, (167.91±6.44) nm and (-27.7±2.6) mV, respectively. The appearance of nanostructured lipid carriers was round or ellipsoidal. The release of freeze-dried powder was in line with Weibull equation model:lnln(1/1-M_t/M_∞)=1.025 1lnt-4.600 4 (r=0.987 5). Luteolin was encapsulated in nanostructured lipid carrier as anamorphous form.CONCLUSION The preparation process of lutelin-nanostructured lipid carriers has a feature of good repeatability, which is worthy of further study.