Hagiwara A, Takahashi T, Kojima O, Yamaguchi T, Sasabe T, Lee M, Sakakura C, Shoubayashi S, Ikada Y, Hyon S H
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Cancer. 1993 Feb 1;71(3):844-50. doi: 10.1002/1097-0142(19930201)71:3<844::aid-cncr2820710330>3.0.co;2-h.
A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), has been developed in dosage form for peritoneal carcinomatosis and has been designed to release 70% of the incorporated cisplatin slowly during a period of 3 weeks. In this study, its pharmacologic effects were examined in rodents.
CDDP-MS was tested to determine (1) tissue distribution of cisplatin after intraperitoneal administration of cisplatin at 3.0 mg/kg body weight to rats, (2) acute toxicity in mice when injected intraperitoneally, and (3) therapeutic effects on peritoneal carcinomatosis induced by transplantable M5076 tumors in mice.
These experiments revealed the following: (1) CDDP-MS resulted in a higher cisplatin concentration in tissues adjacent to the peritoneum for a longer period, and the concentration of cisplatin measured in the rest of the body was lower than that delivered by the cisplatin aqueous solution; (2) the 50% lethal dose value, determined by the Litchfield-Wilcoxon method, was 23.8 mg/kg body weight in CDDP-MS in terms of cisplatin, whereas in the cisplatin aqueous solution it was 13.5 mg/kg body weight; (3) CDDP-MS enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin aqueous solution.
Intraperitoneal CDDP-MS releases cisplatin into the peritoneal cavity for a long time, and it results in less systemic toxicity and greater therapeutic effects on peritoneal carcinomatosis than does cisplatin aqueous solution.
一种新的顺铂药物递送制剂已被开发用于腹膜癌的剂型，其中顺铂被包裹在乳酸低聚物微球（CDDP-MS）中，并设计为在3周内缓慢释放70%的包裹顺铂。在本研究中，对其在啮齿动物中的药理作用进行了研究。
对CDDP-MS进行了测试，以确定（1）给大鼠腹腔注射3.0mg/kg体重顺铂后顺铂的组织分布，（2）腹腔注射时对小鼠的急性毒性，以及（3）对小鼠可移植M5076肿瘤诱导的腹膜癌的治疗效果。
这些实验揭示了以下内容：（1）CDDP-MS在较长时间内导致腹膜附近组织中顺铂浓度更高，而在身体其他部位测得的顺铂浓度低于顺铂水溶液递送的浓度；（2）根据Litchfield-Wilcoxon方法确定，CDDP-MS中顺铂的50%致死剂量值为23.8mg/kg体重，而在顺铂水溶液中为13.5mg/kg体重；（3）与相同毒性剂量的顺铂水溶液相比，CDDP-MS增强了治疗效果。
腹腔注射CDDP-MS可使顺铂在腹腔内长时间释放，与顺铂水溶液相比，它导致的全身毒性更小，对腹膜癌的治疗效果更好。
