ＣＮＤＡＣリン脂質誘導体含有ＲＥＳ回避リポソームの抗腫よう効果

Abstract

2'-C-Cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) has been developed as a novel antitumor nucleoside. 5'-Dipalmitoylphosphatidyl derivative of CNDAC (DPP-CNDAC) also has a significant antitumor activity and is readily incorporated in liposomes. Therefore, to reduce the side effects and to enhance the antitumor activity, we incorporated DPP-CNDAC into reticuloendothelial systems (RES)-avoiding, long circulating, liposomes modified with palmityl-D-glucuronide (PGlcUA), which tend to accumulate passively in tumor tissues. When liposomal DPP-CNDAC modified with PGlcUA was injected intravenously into Meth A sarcoma-bearing mice, it showed higher antitumor activities and increased more the life span of mice, compared to those obtained by injection of DPP-CNDAC only or by liposomal DPP-CNDAC without PGlcUA. Thus, the incorporation of DPP-CNDAC into liposoma membrane modified with PGlcUA may be useful as a formulation of this anticancer agent.