微乳法制备阿昔洛韦固体脂质纳米粒

Preparation of aciclovir solid lipid nanoparticles based on the microemulsion technique

目的:用微乳法制备眼用阿昔洛韦(aciclovir,ACV)固体脂质纳米粒(SLN)。方法:分别以硬脂酸、单硬脂酸甘油酯为油相,以大豆磷脂和吐温80、吐温20为乳化剂,以乙醇、甘油、胆酸钠、十二烷基硫酸钠(SLS)为助乳化剂制备微乳,微乳分散于水中形成SLN。分别考察处方组成和制备工艺对SLN混浊度和稳定性的影响。用微乳法制备的ACV-SLN经冷冻干燥后,观察其重建效果。用原子力显微镜观察ACV-SLN表面的精细结构。结果:使用注射器滴入法和优选处方可以快速制得粒径<150 nm的含1.0%脂质的ACV-SLN混悬液,10 d内保持稳定。ACV-SLN混悬液经冷冻干燥后可重建。结论:微乳法制备ACV-SLN,简单快捷,不需使用有机溶剂(如二氯甲烷、氯仿等)和复杂设备,适合SLN的研究和小规模制备。

Objective： To prepare the aciclovir （ACV） solid lipid nanoparticles （SLN） for eye use based on the microemulsion technique. Methods： Stearic acid, glycerol monostearate were selected as oil phase, tween 80, tween 20 and soy lecithin as emulsifier, and ethanol, glycerol, sodium cholate, sodium lauric sulfate as co-emulsifier respectively to prepare the oil-in-water microemulsions. Microemulsions dispersed into water and then SLNs were generated. Influences of formulation components and preparation procedures on turbidity and stability of SLN were investigated to optimize the best formula and preparation methods. ACV-SLNs prepared by the microemulsion methods were lyophilized, and its reconstruction effect was evaluated. The fine structure of ACV-SLN surface was observed by atomic force microscope （AFM）. Results： ACV-SLN suspensions containing 1.0% lipid with the diameter less than 150 nm were rapidly prepared by dropping method with an injector and the optimal formula, which were stable within 10 d. ACV-SLN suspensions could be reconstituted with water after lyophilized. Conclusion： The preparation of ACV-SLN with microemulsion technique is rapid and simple. Toxic organic solvents （such as dichloromethane, chloroform） and complicated machines are not involved in the process. This method is suitable for the researches and the small-scale preparation of SLN.