Schwendener R A, Schott H, Hartmann H R, Supersaxo A, Rubas W, Hengartner H
Institut für Pathologie, Universitätsspital, Zürich.
Onkologie. 1987 Aug;10(4):232-9. doi: 10.1159/000216411.
A method of preparation for large volumes of sterile, homogenous bilayer liposomes as carriers of lipophilic cytostatic prodrugs is described. Liposomes in the size range of 60 to 120 nanometers are produced through the dialysis of lipid/prodrug/detergent micelles by means of a capillary dialysis system. The cytostatic effect of cytosine arabinoside (ara-C) prodrug liposomes against L1210 leukemia showed to be superior to free ara-C treatment in respect to drug dosage and treatment schedule. Fluorodeoxyuridine (FUdR) prodrug-liposomes were active against various solid tumors, although with less pronounced effects, but at 20-60 times lower drug concentrations as compared to free FUdR. To further improve the cytostatic effect of such prodrug-containing liposomes, methods for the linkage of tumor-cell-specific antibodies to the liposomes are discussed. The targeted delivery of cytostatic drugs by such means might improve their antitumor effects and reduce the untoward toxic side-effects.
描述了一种制备大量无菌、均匀双层脂质体作为亲脂性细胞抑制前药载体的方法。通过毛细管透析系统对脂质/前药/去污剂胶束进行透析，制备出尺寸范围为60至120纳米的脂质体。阿糖胞苷（ara-C）前药脂质体对L1210白血病的细胞抑制作用在药物剂量和治疗方案方面均优于游离阿糖胞苷治疗。氟脱氧尿苷（FUdR）前药脂质体对各种实体瘤有活性，尽管效果不太明显，但与游离FUdR相比，药物浓度低20至60倍。为了进一步提高此类含前药脂质体的细胞抑制作用，讨论了将肿瘤细胞特异性抗体与脂质体连接的方法。通过这种方式靶向递送细胞抑制药物可能会提高其抗肿瘤效果并减少不良毒性副作用。
