PEG修饰脂质体对阿霉素载药量的影响

目的:在以阿霉素为模型药物用复乳法制备PEG修饰脂质体实验中,发现当制备完毕立即上柱分离时,包封率约为50%;但当样品放置过夜后再测包封率却为98%.本文通过实验分析该现象产生的原因.方法:用不同方法制备PEG修饰的空白脂质体,考察是否仍能吸附阿霉素;制备无PEG修饰的空白脂质体,考察对阿霉素有无吸附作用;设计不同的PEG-阿霉素配比,在不同的孵育时间取样测定对阿霉素的吸附量;将阿霉素溶液直接与PEG20000混合孵育,考察无脂质体时PEG对阿霉素的吸附; 另选土霉素为模型药物,考察是否仍然存在吸附作用.结果:不同方法制备的PEG修饰的空白脂质体对阿霉素都有吸附;无PEG修饰的空白脂质体对阿霉素无吸附作用;PEG对阿霉素的吸附进程受PEG-阿霉素配比、孵育时间的影响;单独的PEG20000对阿霉素也能很好地吸附; 以土霉素代替阿霉素,这种吸附作用仍然存在.结论:该现象是由于PEG链对体相中阿霉素或土霉素的吸附而引起的;这种吸附可能是阿霉素的羟基或氨基对PEG链上氧原子之间的氢键作用.提示这种相互作用的存在能够提高PEG修饰的长循环脂质体,以及含PEG材料的微囊、微球等对这类多羟基或多氨基小分子药物的载药量.

The effect of PEG-modified liposomes on adriamycin entrapment

SUMMARY Objective:To analyse the reason for a strange phenomenon in adriamycin entrapment by liposomes prepared by double emulsion method.Methods:PEG modified blank liposomes were prepared by different methods, and blank liposomes without PEG modification were also prepared in order to see whether the similar phenomenon would occur;different PEG adriamycin ratios and different incubation times were designed to observe their effect on absorption;mixture composed of PEG 20000 and adriamycin was dialysed to find the absorption between PEG itself and adriamycin.Results:The phenomenon was unaffected by preparation method and liposome itself, but only affected by the presence of PEG chains around PEG modified liposomes;both the PEG adriamycin ratio and incubation time affected the absorption of adriamycin to PEG;the PEG alone could absorb adriamycin well; the absorption occurred when oxytetracycline was in place of adriamycin.Conclusion:The reason for the phenomenon was the absorption of adriamycin or oxytetracycline molecules to PEG chains where multiple hydrogen bonds might be formed. It is suggested PEG modified liposomes or PEG containing carriers such as microencapsules and microspheres would increase the entrapment efficiency or carrying amount of this kind of low molecular drugs which contain a number of hydroxies or aminos.