环孢素A固体脂质纳米粒的制备与理化性质考察

Studies on preparation of cyclosporin SLN and its physical-chemical properties

目的探讨以环孢素(cyclosporin A,CyA)为模型药物的多肽类药物固体脂质纳米粒(SLN)的制备并研究其理化性质方法以CyA为模型药物,选用甘油三硬脂酸酯,采用溶剂扩散法制备甘油三酸酯纳米粒,测定其粒径分布、表面电位、药物包封率考察不同的制备工艺对SLN粒径及包封率的影响,并进行载药纳米粒的体外释放实验结果以CyA为模型药物,用水性溶剂扩散法可以简便、快速制得甘油三硬脂酸酯固体脂质纳米粒,体均粒径为(142.5±120.2)nm,包封率为58.42% 并且通过调节pH的方法,在高速离心(25 000 r·min-1)条件下,即可达到纳米粒与分散体系之间的有效分离甘油三硬脂酸酯纳米粒在最初的6 h有药物的突释现象,在随后的8 d内药物的释放明显减缓,每天释放约药物总量的5.7% 加入5%和10%聚乙二醇(PEG)的SLN能明显加快药物的释放。结论经溶剂扩散法制备并通过加入一定比例PEG。

OBJECTIVE: To study the preparation and physicochemical characteristics of cyclosporin SLN. METHODS: A stable SLN was prepared using triglyceride by solvent diffusion method in aqueous system. The lipophilic model drug, cyclosporin, was incorporated. The entrapment efficacy, Zeta potential (charge), drug delivery characterization were measured. Various preparation processes of SLN were carried out to investigate their effect on particle size, entrapment efficacy and drug release profiles of SLN. RESULTS: Triglyceride solid lipid nanoparticles were quickly prepared by a novel solvent diffusion method in aqueous system. The particles prepared under the condition of ice bath exhibited satisfied particle size and relatively high entrapment efficacy. SLN was separated completely by the centrifuge of 25 000 r &middot min-1 in the acidic dispersed aqueous medium. After burst release at the beginning, a prolonged release was observed. More rapid release profile was achieved by adding 5% and 10% polyethylene glycol (PEG) in SLN in vitro. CONCLUSION: The solid lipid nanoparticles prepared by solvent diffusion method can deliver cyclosporin in a controlled manner.