Toxicities in rats with free versus liposomal encapsulated cisplatin.
Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1 or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution intraperitoneally biweekly for 15 injections. Rats in the free drug group showed significantly less weight gain; two rats died during the study. At necropsy, the free cisplatin--treated rats showed gross and microscopic evidence of peritoneal fibrosis that was not detected in any of the remaining groups. The free cisplatin--treated rats showed serum and histologic evidence of renal damage; all five rats had moderate or severe acute tubular necrosis. No renal abnormalities were detected in rats that received 1 mg/kg, and only focal or mild changes were found in rats that received 2 mg/kg of the liposomal preparation. Neurotoxicity, as determined by nerve conduction and inclined plane studies, developed in rats treated with free and liposomal cisplatin. These results are encouraging and warrant further investigation.
Potkul
R K
RK
Department of Obstetrics and Gynecology, Georgetown University School of Medicine, Washington, DC 20007.
Gondal
J
J
Bitterman
P
P
Dretchen
K L
KL
Rahman
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004337:Drug Carriers; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D007274:Injections, Intraperitoneal / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008081:Liposomes; D009431:Neural Conduction / Q000187:drug effects; D010537:Peritoneum / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004337:Drug Carriers; D008081:Liposomes; D002945:Cisplatin