高温乳化-低温固化法制备芦丁固体脂质纳米粒及理化性质分析

Preparation of Rutin-loaded Solid Lipid Nanoparticles Using Emulsion Evaporation at a High temperature and Solidification at a low Temperature and Their Physicochemical Properties

目的观察高温乳化-低温固化法制备的芦丁固体脂质纳米粒(RT-SLN)的理化性质及体外释药特性。方法以硬脂酸为脂质材料,采用高温乳化-低温固化法制备芦丁固体脂质纳米粒,以均匀设计法优化处方及制备工艺,并对其形态、粒径、Zeta电位、包封率(EE)、体外释药特征等进行评价。结果所制备的RT-SLN外观呈类球形,粒径为(192.47±31.8)nm,Zeta电位(-18.90±0.27)mV。以EE为评价指标表进行处方筛选,回归方程计算得优化工艺为药物-硬脂酸比1∶4,硬脂酸用量200mg,聚山梨酯-80浓度12mg/ml,聚乙二醇-400浓度5%、转速1500r/min,初乳与分散相体积比为1∶7,预测优化值为90.11%,其95%的可信区间为83.71%～96.51%,平均EE(89.34±0.93)%。72h药物累积释放约85%,体外释药符合Higuchi方程:Q=8.345t1/2+15.023(r=0.9892)。结论高温乳化-低温固化法适于制备RT-SLN,制备的RT-SLN具有缓释作用,能提供平稳的血药浓度,利于提高患者的用药依从性。

Objective To prepare rutin-loaded solid lipid nanoparticles （RT-SLN） using emulsion evaporation at a high temperature and solidification at a low temperature and investigate its physicochemical properties and release behavior in vitro. Methods RT-SLN was prepared with the method of emulsion evaporation at a high temperature and solidification at a low temperature. Stearic acid with high biocompatibility was used as lipid carrier. The optimum formulation was selected by uniform design, the morphology, particle size and size distribution, Zeta potential, entrapment efficiency（EE） and release behavior in vitro were evaluated. Results The obtained RT-SLN was spherical with mean particle size of （ 192.47 ＋ 31.8） rim, Zeta potential of （ - 18.90 ＋_0.27） mV. The formulation using the EE as the indicator was screened and the optimized procedure parameters were obtained： drug-stearic acid 1： 4, stearic acid amount 200 mg, Tween-80 concentration 12 mg/ml, PEG-400 concentration 5% , rotation rate 1500 rpm, the ration of volume of coarse emulsion and disperse phase was 1： 7, the calculated EE was 90.11% （95% confidence interval： 83.71% -96.51% ）, the average EE was （89.34 ＋ 0.93 ） %. The in vitro release profile of the nanopartilces was expressed well by Higuchi equation ： Q = 8. 345 t1/2 ＋ 15. 023（r = 0.9892）, 85% was released at 72 h. Conclusion RT-SLN with sustained released property can be prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature. RT-SLN can lead to steady blood curve which is beneficial for the patients＇s compliance.