Tokudome Y, Oku N, Doi K, Namba Y, Okada S
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Biochim Biophys Acta. 1996 Feb 21;1279(1):70-4. doi: 10.1016/0005-2736(95)00242-1.
Liposomes modified with the uronic acid derivative palmityl-D-glucuronide (PGlcUA) have a long circulation time and tend to accumulate in the tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 4:4:1 as a molar ratio) on tumor-bearing mice. VCR was loaded into liposomes by a remote loading method, and then free or liposomal VCR was injected intravenously into BALB/c mice bearing Meth A sarcoma implanted subcutaneously 5 days before hand. Single-dose administration of VCR (3.0 mg/kg) in PGlcUA-liposomes significantly suppressed tumor growth, and prolonged the survival time (T/C = 1.37). Furthermore, two-dose administration of the liposomes cured one third of the animals. The therapeutic effect of PGlcUA-liposomes was greater than that of control liposomes containing dipalmitoylphosphatidylglycerol instead of PGlcUA. PGlcUA-liposomes might thus be a useful tool for delivering antitumor agents to tumor tissues.
用糖醛酸衍生物棕榈酰-D-葡萄糖醛酸（PGlcUA）修饰的脂质体具有较长的循环时间，并且倾向于在荷瘤小鼠的肿瘤中蓄积。利用这一特性，我们研究了包裹在含有PGlcUA的脂质体（二棕榈酰磷脂酰胆碱/胆固醇/PGlcUA的摩尔比为4:4:1）中的长春新碱（VCR）对荷瘤小鼠的治疗效果。通过远程载入法将VCR载入脂质体，然后在预先5天皮下植入Meth A肉瘤的BALB/c小鼠中静脉注射游离的或脂质体包裹的VCR。单剂量给予PGlcUA脂质体中的VCR（3.0 mg/kg）可显著抑制肿瘤生长，并延长生存时间（T/C = 1.37）。此外，两剂量给予脂质体可使三分之一的动物治愈。PGlcUA脂质体的治疗效果优于含有二棕榈酰磷脂酰甘油而非PGlcUA的对照脂质体。因此，PGlcUA脂质体可能是一种将抗肿瘤药物递送至肿瘤组织的有用工具。
