Tokuda K, Natsugoe S, Shimada M, Kumanohoso T, Baba M, Takao S, Nakamura K, Yamada K, Yoshizawa H, Hatate Y, Aikou T
First Department of Surgery, Kagoshima University School of Medicine, Japan.
Int J Cancer. 1998 May 29;76(5):709-12. doi: 10.1002/(sici)1097-0215(19980529)76:5<709::aid-ijc16>3.0.co;2-z.
Microspheres containing cisplatin (CDDP) embedded in poly-d,l-lactic acid (PLA) and polyethylene glycol acid (CDDP-PPMS) were developed to improve treatment of malignant effusions. In vitro studies demonstrated that CDDP was released continuously for more than 4 weeks from CDDP-PPMS without initial burst. CDDP-PPMS was compared with CDDP aqueous solution (CDDP-SOL) by i.p. administration in rats for 1) tissue distribution, 2) toxicity and 3) therapeutic effects against Yoshida sarcoma. We found that the CDDP concentration in the omentum was maintained at a higher level than in the CDDP-SOL group, while the particles of CDDP-PPMS were observed in the stomata of the omentum by electron microscopy. Concentrations of CDDP in the lung, liver, kidney and blood were lower in the CDDP-PPMS group than in the CDDP-SOL group. All rats given CDDP-PPMS containing < or = 28 mg/kg were alive, whereas in the CDDP-SOL group, all rats given > or = 16 mg/kg died from side effects. The LD50 of CDDP-PPMS and CDDP-SOL were 32.8 and 14.8 mg/kg, respectively. The survival of rats with peritoneal metastasis was better in the CDDP-PPMS group than in the CDDP-SOL group.
为了改善恶性积液的治疗效果，研制了一种将顺铂（CDDP）包埋于聚-d，l-乳酸（PLA）和聚乙醇酸（CDDP-PPMS）中的微球。体外研究表明，CDDP从CDDP-PPMS中持续释放超过4周，无初始突释。通过腹腔注射将CDDP-PPMS与顺铂水溶液（CDDP-SOL）在大鼠中进行比较，以研究1）组织分布、2）毒性和3）对吉田肉瘤的治疗效果。我们发现，大网膜中CDDP的浓度维持在高于CDDP-SOL组的水平，而通过电子显微镜观察到CDDP-PPMS颗粒存在于大网膜的气孔中。CDDP-PPMS组肺、肝、肾和血液中CDDP的浓度低于CDDP-SOL组。所有给予含≤28mg/kg CDDP-PPMS的大鼠均存活，而在CDDP-SOL组中，所有给予≥16mg/kg的大鼠均死于副作用。CDDP-PPMS和CDDP-SOL的半数致死量分别为32.8和14.8mg/kg。CDDP-PPMS组腹膜转移大鼠的生存期优于CDDP-SOL组。
