Yokoyama M, Okano T, Sakurai Y, Ekimoto H, Shibazaki C, Kataoka K
Institute of Biomedical Engineering, Tokyo Women's Medical College, Japan.
Cancer Res. 1991 Jun 15;51(12):3229-36.
Toxicity and in vivo antitumor activity against five solid tumors (C 26, C 38, M 5076, MKN-45, MX-1) of Adriamycin (ADR)-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer (PEG-P[Asp(ADR)]) were evaluated, and its pharmacokinetic behavior in blood and biodistribution by i.v. injection were obtained. PEG-P[Asp(ADR)] was revealed to express higher antitumor activity than ADR against all the examined tumors except MKN-45. Especially against C 26, PEG-P[Asp(ADR)] expressed critical suppression of tumor growth and considerably prolonged life span of the treated mice. PEG-P[Asp(ADR)] was observed in blood at much higher concentrations with a longer half-life than ADR after the i.v. injection. PEG-P[Asp(ADR)] was known to form a micellar structure with a diameter of approximately 50 nm and a narrow distribution in phosphate-buffered saline. Therefore, the stabilized circulation of ADR residue in blood by binding to the block copolymer was considered to result from the micellar structure which possesses the hydrated outer shell composed of the poly(ethylene glycol) chains.
评估了阿霉素（ADR）共轭聚乙二醇-聚天冬氨酸嵌段共聚物（PEG-P[Asp(ADR)]）对五种实体瘤（C 26、C 38、M 5076、MKN-45、MX-1）的毒性和体内抗肿瘤活性，并通过静脉注射获得了其在血液中的药代动力学行为和生物分布。结果显示，除MKN-45外，PEG-P[Asp(ADR)]对所有检测肿瘤的抗肿瘤活性均高于ADR。特别是对于C 26，PEG-P[Asp(ADR)]表现出对肿瘤生长的显著抑制作用，并显著延长了治疗小鼠的寿命。静脉注射后，PEG-P[Asp(ADR)]在血液中的浓度比ADR高得多，半衰期也更长。已知PEG-P[Asp(ADR)]在磷酸盐缓冲盐水中形成直径约为50 nm且分布狭窄的胶束结构。因此，ADR残基通过与嵌段共聚物结合而在血液中稳定循环被认为是由具有由聚乙二醇链组成的水合外壳的胶束结构所致。
