【摘要】 目的:制备他克莫司类脂囊泡(Tac-NS)并进行体外表征。方法:采用薄膜水化-超声法制备Tac-NS。以包封率(EE%)、载药量、平均粒径及粒径分布(PDI)的综合评分为指标,设计正交试验对硬脂山梨坦(Span-60)浓度、Span-60与胆固醇的摩尔比、Span-60与脱氧胆酸钠(SDC)的摩尔比进行优化。考察所制Tac-NS的外观形态、平均粒径、PDI、Zeta电位及EE%,并通过体外经皮渗透试验比较Tac-NS与Tac和NS物理混合物的累积经皮渗透量(Q)、累积皮肤滞留量(Qs)。结果:最优处方为Span-60 0.025mol/L,Span-60与胆固醇的摩尔比10∶1,Span-60与SDC的摩尔比15∶1,药载比5%。所制Tac-NS形态圆整、分散均匀、很少有聚集,平均粒径为(233.0±6.48)nm,PDI为0.266±0.021,Zeta电位为(-41.7±0.32)m V,EE%为(76.83±4.61)%。经皮渗透试验表明,24 h后Tac-NS的Qs值约为物理混合物的2.4倍,而二者Q值相当。结论:成功制得EE%高、粒径小、分布均匀、透皮效果较为理想的Tac-NS。更多还原

【Abstract】 OBJECTIVE:To prepare Tacrolimus niosomes(Tac-NS) and evaluate their characteristics in vitro. METHODS:Tac-NS were prepared by a film hydration-ultrasonic method. Using the comprehensive score of encapsulation efficiency(EE%),drug-loading amount,mean particle size and PDI as the evaluation index,orthogonal design was used to optimize the concentration of sorbitan monostearate(Span-60),mole ratio of Span-60 to cholesterol,mole ratio of Span-60 to SDC. The morphology,mean particle size,PDI,Zeta-potential and EE% of Tac-NS were investigated. Accumulative percutaneous penetration(Q)and accumulative retention amount(Qs)of Tac-NS and physical mixture of Tac and NS were compared by percutaneous penetration test in vitro.RESULTS:The optimal formulation was as follows as Span-60 0.025 mol/L,mole ratio of Span-60 to cholesterol 10 ∶ 1,mole ratio of Span-60 to SDC 15 ∶ 1,drug-loading amount of 5%. Tac-NS was spherical and distributed evenly,but hardly congregated.The mean particle size,PDI,Zeta-potential and EE% were(233.0 ± 6.48) nm,0.266 ± 0.021,(-41.7 ± 0.32) m V and(76.83 ±4.61)%,respectively. The results of in vitro permeability study showed that Qsof Tac-NS was 2.4 times of physical mixture;in addition,Q of the two were similar. CONCLUSIONS:Tac-NS,owning high EE%,small particle size,uniform distribution and ideal permeation effect,is prepared successfully.更多还原