摘要
目的制备吴茱萸碱磷脂复合物,表征其理化性质,并初步考察其体外抗肿瘤活性。方法采用溶剂挥发法制备吴茱萸碱磷脂复合物,用星点设计-效应面法优化其制备工艺,并考察其表观溶解度、粒径和Zeta电位,用红外光谱仪和综合热分析仪了复合物的形成机制,MTT实验考察其体外抗肿瘤活性。结果优化的磷脂复合物制备工艺为:以体积分数为50%的乙醇和四氢呋喃的混合溶液作为反应溶剂,磷脂与吴茱萸碱的投药分子比为2∶1,吴茱萸碱的反应浓度为2.5 mg.mL-1,反应温度和反应时间分别为60℃和3 h,复合率可达94.15%,吴茱萸碱磷脂复合物在水中的溶解度提高到原料药的3.4倍,其粒径和Zeta电位分别为243.4 nm和-44.21 mV,IR和DSC分析结果提示,吴茱萸碱和磷脂之间存在非极性相互作用,MTT实验表明,制备成复合物后EVO的体外抗肿瘤活性有所降低,表现出折中效应。结论本实验成功制备了吴茱萸碱磷脂复合物,工艺简单、可行,复合率高,制剂水溶性有所改善,为吴茱萸碱的制剂学研究提供了参考。
OBJECTIVE To prepare evodiamine phospholipids complex, investigate its physicochemical properties and study its anti-tumor activities in vitro. METHODS Evodiamine phospholipids complex was prepared and optimized by solvent evaporation method and central composite design, physieochemical characteristics of the complex were investigated by means of apparent solubility studies,fourier transform infrared spectroscopy（FT＇-IR） and differential scanning calorimetry （DSC） , the Particle size and zeta-potential were also investigated. MTT assay was employed to evaluate the anti-tumor activities of the complex in vitro. RESULTS The optimal formulation protocol for evodiamine phospholipids complex were as follows：mixture （1：1 ,v/v） of ethanol and tetrahydrofuran was taken as the reaction medium, phospholipids-to-evodiamine molar ratio, reaction concentration of evodiamine, reaction temperature and time were 2： 1,2. 5 mg . mL-1 ,60℃ and 3 h,respectively. The complex rate,particle size and Zeta potential for the optimized EVO- PLC was 94. 15% ,243.4 nm and -44. 21 mV ,respectively. IR and DSC analysis indicated that evodiamine might interact with phospholipids by apolar interactions. MTT assay showed that the anti-tumor activities of evodiamine phospholipids complex on LLC cells was less effective than evodiamine in vitro. CONCLUSION Evodiamine phospholipids complex was successfully developed under the optimized protocol, possessing high complex rate and enhanced solubility in water, which was a fundamental formulation for the further research of evodiamine.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2012年第7期517-523,共7页
Chinese Pharmaceutical Journal
基金
教育部博士点基金资助项目(20095503120008)
重庆市教育委员会资助项目(首批高等学校优秀人才资助
KJ090308)
关键词
吴茱萸碱
磷脂复合物
抗肿瘤活性
星点设计
evodiamine
phospholipids complex
anti-tumor activity
central composite design
