Low toxicity and anticancer activity of a novel liposomal cisplatin (Lipoplatin) in mouse xenografts.
Cisplatin has been one of the most widely used and most effective cytotoxic agents in the treatment of malignancies but causes severe adverse reactions including nausea/vomiting, renal toxicity, gastrointestinal toxicity, peripheral neuropathy, asthenia, and ototoxicity. A liposomal formulation of cisplatin, Lipoplatin, was developed in order to reduce the systemic toxicity of cisplatin. A single treatment of rats with 30 mg/kg Lipoplatin resulted in no toxicity whereas 2 or 3 weekly administrations at 30 mg/kg to rats gave neutropenia but no nephrotoxicity. On the contrary, a single injection to rats of 5 mg/kg cisplatin resulted in severe nephrotoxicity. Thus, Lipoplatin is less toxic than cisplatin in rats. Intraperitoneal or intravenous injection of Lipoplatin to SCID (severe combined immunodeficient) mice with subcutaneous breast MCF-7 or prostate LNCaP human tumors resulted in size reduction of the tumors; histological examination of the treated tumors in xenografts was consistent with apoptosis in tumor cells; thus, Lipoplatin appears to exert its cytotoxic effects to tumors in a mechanism similar to that of cisplatin. The preclinical studies reported here set the foundation for the clinical use of Lipoplatin as an exciting new drug with lower toxicity than cisplatin, endowed with proapoptotic properties.
Boulikas
Teni
T
Regulon, Inc., Mountain View, CA 94043, USA. teni@regulon.org
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014183:Transplantation, Heterologous
D004337:Drug Carriers; D008081:Liposomes; C503131:lipoplatin; D002945:Cisplatin