香叶木素脂质体的处方优化及其体外释放

Formulation Optimization and in vitro Release of Diosmetin Liposomes

为改善香叶木素的水溶性,采用薄膜超声分散法制备其脂质体,并首先以包封率、粒径为指标进行单因素试验初步筛选处方和工艺参数,再通过Box-Behnken设计-响应面法进一步优化。结果表明,所得的香叶木素脂质体优化处方工艺如下:脂药比(即大豆磷脂与香叶木素的质量比)5.26、胆固醇质量6.31 mg、水化后磷脂浓度1.19 mg/ml,在超声功率为360 W、超声时间为2 min的条件下制备。优化的香叶木素脂质体粒径为(146±3)nm,ζ电位为(–38.63±0.13)mV,包封率为(88.2±1.2)%,载药量为14.6%。透射电镜照片显示所得脂质体大小均一,呈球形。体外释放试验中,48 h累积释放率为79.68%,释放行为结果符合Weibull方程(r=0.9950)。

The liposomes loaded with diosmetin were prepared by thin film ultrasonic dispersion method to improve poor water-soluble of diosmetin.With encapsulation efficiency and particle size as main indicators,single factor tests were carried out to find the test ranges of formulation and process parameters,followed by further optimization with response surface methodology coupled with Box-Behnken design.The optimal formulation and process parameters were as follows:lipid-drug ratio(namely the mass ratio of soybean phospholipids to diosmetin)was 5.26,cholesterol mass was 6.31 mg,and phospholipid concentration after hydration was 1.19 mg/ml,ultrasonic treatment of the obtained hydration liquid was conducted at 360 W for 2 min.The particle size,ζpotential,encapsulation efficiency and drug loading of the final diosmetin liposomes were(146±3)nm,(–38.63±0.13)mV,(88.2±1.2)%and 14.6%,respectively.The transmission electron microscopy analysis revealed that the liposomes were uniform in size and spherical in shape.The in vitro cumulative release at 48 h was 79.68%,and the diosmetin release behavior was conformed to the Weibull's equation(r=0.9950).