冻干保护剂对hb有效组分脂质体包封率和粒径的影响.docVIP

冻干保护剂对HB有效组分脂质体包封率和粒径的影响 nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; 作者：刘娟 胡水根nbsp;nbsp;卞俊 汪国华 柯乾坤 【摘要】nbsp; 目的研究不同冻干保护剂种类和浓度对HB有效组分脂质体冻干前后包封率和平均粒径的影响。方法按16个处方制备了HB有效组分脂质体，采用荧光分光光度法测定包封率，用显微镜和数码图象分析软件测定了平均粒径，通过冻干前后脂质体包封率和粒径的比较优选出最佳的冻干保护剂。结果最佳冻干保护剂为甘露醇和二元保护剂蔗糖-甘氨酸，包封率达到69.91%和66.70%，外观效果良好，比例分别为，甘露醇∶PC∶CH∶HB = 4∶1∶0.5∶0.2；蔗糖∶甘氨酸∶PC∶CH∶HB = 4∶0.8∶1∶0.5∶0.2。结论 冻干保护剂可减少脂质体囊泡在冻干过程受到的破坏以及对脂质体包封率和粒径的影响。 【关键词】nbsp; 脂质体 冻干保护剂 包封率 粒径 　　Abstract：ObjectiveTo study the effects of freeze-drying on the endcapsulation and vesicles size of HB liposome with different kinds of lyoprotectents at various concentrations.MethodsSixteen formulations of HB liposome were designed.The entrapment efficiency was examined by fluorospectrophotometry.The particle size of the preparation was examined by microscope and digital imaging analysis software.The optimized lyoprotectent was selected based on the comparison of entrapment efficiency and particle size before and after freeze-drying.ResultsThe use of sucrose as a primary lyoprotectent and glycine as a supporting lyoprotectents and the use of mannitol provided the highest encapsulation rate and minimal change of HB liposomes.The results showed that the optimum formula were Man∶PC∶CH∶HB = 4∶1∶0.5∶0.2; Suc∶Gly∶PC∶CH∶HB = 4∶0.8∶1∶0.5∶0.2,the encapsulation rates were 69.91% and 66.70%.ConclusionThe lyoprotectent can protect the liposome vesicles during freeze-drying and mininal the influences of encapsulation and particle size. 　　Key words：Liposome;nbsp; Lyoprotectents;nbsp; Entrapment efficiency；nbsp; Particle size nbsp;nbsp;nbsp; 　　HB有效组分是从海洋湖沼类贝壳软体动物园背角无齿蚌anodonta woodiana (Lea)中提取的一组具抗肿瘤活性的糖蛋白类物质。将该有效组分制成了脂质体后，经小鼠移植性肿瘤体内实验表明，口服具有抗肿瘤活性，对S180肉瘤，Lewis肺癌，黑色素B16肺转移癌的抑瘤率分别为48.76%,54.38%,52.66%［1］。但液态的HB有效组分脂质体是混悬乳剂，只能贮存几周［2］，在50℃以上的介质环境中，结构不稳定，磷酯双分子层结构易氧化破坏，不仅影响药物包封率，且生成的溶血磷脂会危害机体［3］。为使脂质体能在常温下长期稳定贮存，近年来广泛用冷冻干燥技术制备冻干品。冷冻干燥法是目前制备储存脂质体的最佳方法。但在冷冻过程形成的冰晶使脂质体聚集融合，在冷冻和解冻过程中，膜内外冰晶形成速度不同引起渗透压差，造成脂质体裂解，