Objective To prepare amphiphilic derivatives of nucleotide drugs and their self-assemblies. Methods 3'-hydroxyurea-deoxythymidine lipid esters were synthesized. The amphiphilic prodrugs were investigated using a Langmuir trough to confirm the effect of different lipid chains. Self-assemblies were prepared using the injection method and the morphologies and particle sizes were measured. Results The derivatives were prepared with zidovudine and the C8, C14, C16, C18-chained fatty acids. The surface pressure-molecular area (p-a) curves of the derivatives were determined by the length ratio of heads to lipid chains. The long-chained derivatives tended to be erect to on the surface, while the short-chained derivatives were easy to squeeze into water. The self-assemblies of derivatives showed the morphologies from irregular vesicle to nanotubes with a mean size of 100 nm to 400 nm. Conclusion The self-assembling nature of amphiphilic derivatives depends on the ratio of heads to lipid chains. The self-assembly is a promising drug delivery system.%目的 制备系列核苷药物两亲性衍生物的自组装体.方法 合成具有潜在生物活性的3’-羟基脲3’-脱氧胸苷脂肪酸酯,用Langmuir膜天平考察不同长度脂肪链对前药分子单分子膜的影响.用注入法制备自组装体,透射电子显微镜观测其形态和粒径.结果 以齐多夫定为原料制备得到脂肪链长度分别为C8、C14、C16、C18的衍生物分子.它们在水-空气界面上的表面压-分子面积(π-a)曲线形态由极性头和脂肪链长度的比例决定.长脂肪链的衍生物分子易在水面上直立,短链分子易被挤入水中.随脂肪链增长,自组装体形态为不规则囊泡到纳米管,平均粒径为100～ 400 nm.结论 两亲性衍生物的自组装性由疏水链和极性头比例决定.本研究得到的自组装体有望成为新型纳米给药系统.
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