Schwendener R A, Supersaxo A, Rubas W, Weder H G, Hartmann H R, Schott H, Ziegler A, Hengartner H
Biochem Biophys Res Commun. 1985 Jan 31;126(2):660-6. doi: 10.1016/0006-291x(85)90235-9.
5'-O-palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine were prepared by the reaction of 5-fluoro-2'-deoxyuridine in dimethylacetamide with palmitic acid chloride. The incorporation of the synthesized prodrugs into liposomes composed of egg phosphatidylcholine/stearylamine/cholesterol/alpha-tocopherol at a molar ratio of 10:1:2:0.05 was nearly quantitative; homogeneous bilayer vesicles (75 nm diameter) were obtained. Preliminary tolerance studies revealed that the prodrug-liposome preparations are about 20-60 times more toxic than the parent drug. The prodrugs incorporated into liposomes were 10 to 30 times more active against murine colon 38 carcinoma compared to the free drug. In comparison to the administration of the prodrugs in peanut oil the liposomal preparations seem to exert improved effects and represent a valuable drug delivery system for parenteral applications.
5'-O-棕榈酰基-和3',5'-O-二棕榈酰基-5-氟-2'-脱氧尿苷是通过5-氟-2'-脱氧尿苷在二甲基乙酰胺中与棕榈酰氯反应制备的。将合成的前药以10:1:2:0.05的摩尔比掺入由鸡蛋磷脂酰胆碱/硬脂胺/胆固醇/α-生育酚组成的脂质体中几乎是定量的；获得了均匀的双层囊泡（直径75nm）。初步耐受性研究表明，前药脂质体制剂的毒性比母体药物高约20-60倍。与游离药物相比，掺入脂质体中的前药对小鼠结肠38癌的活性高10至30倍。与在前花生油中给药前药相比，脂质体制剂似乎具有更好的效果，并且是用于肠胃外应用的有价值的药物递送系统。
