复乳冻干法制备甲氨蝶呤囊泡

Preparation of Methotrexate Niosomes Using Freeze-Drying of Double Emulsions Method

目的采用复乳冻干法制备非离子表面活性剂囊泡,研究囊泡对水溶性药物甲氨蝶呤的包封作用。方法以非离子表面活性剂Span60、胆固醇、聚乙二醇6000为囊材,采用复乳冻干法制备甲氨蝶呤囊泡,通过正交实验设计优化其制备工艺,并利用光散射技术测定其粒度分布及Zeta电位值,考察了载药囊泡的包封率、稳定性及其体外释放情况。结果采用复乳冻干法制备出的非离子表面活性囊泡粒度分布均匀、具有良好的稳定性及复溶性,对甲氨蝶呤包封率可高达83.71%。体外释放实验显示,5 h时,游离药物释放完全,而囊泡中甲氨蝶呤的累计释放率仅达到50%,囊泡具有明显的缓释性能。结论复乳冻干法是制备非离子表面活性剂囊泡的一种可靠、有效的方法,为囊泡载药体系的储存、运输及推广应用奠定了基础。

OBJECTIVE To prepare nonionic surfactant niosomes by multiple emulsion freeze-drying method and study their en- capsulation effects for the water-soluble drug, methotrexate. METHODS Using nonionic surfactants Span60, cholesterol, or PEG 6000 as capsule material, methotrexate niosomes were prepared by the method of multiple emulsion lyophilization. The preparation process was optimized, and the niosomes＇ physicochemical properties, entrapment efficiency, stability and in vitro release were investigated. RESULTS The prepared niosomes had uniform particle size distribution and relatively high entrapment efficiency, and the maximum encapsulation efficiency of methotrexate reached 83. 71%. The lyophilized product of niosomes had good stability and solubility. The in vitro release experiment showed that the free drug released completely after 5 h, while the cumulative release rate of methotrexate in the niosomes reached only 50%, which indicated the sustained release effect of niosomes. CONCLUSION Multiple emulsion lyophilization is an effective method for the preparation of nonionic surfactant niosomes, which provides a new choice for the development of a novel drug delivery system.