Multivesicular liposomes containing cytarabine entrapped in the presence of hydrochloric acid for intracavitary chemotherapy.
For a full exploitation of the 1000-fold ip pharmacokinetic advantage obtained when cytarabine is administered ip, the drug exposure must be prolonged because the drug is a cell cycle phase-specific agent. Multivesicular liposomes made from nontoxic components were studied as biodegradable, slow-release microcapsules for intracavitary therapy. No attempt was made to increase efficacy by fusing liposomal membrane with that of tumor cells or by selective targeting of liposomes to cancer cells other than simple administration into a cavity. The presence of HCl with cytarabine at the time of encapsulation was found to decrease the leakage rate in human plasma dramatically. After ip administration of encapsulated cytarabine to mice, the total intracavitary drug concentration initially increased tenfold in 15 hours, then fell to the original concentration at 87 hours. The total amount of the drug in the peritoneal cavity decreased with a 21-hour half-life. All mice treated 24 hours after ip inoculation with 1 X 10(6) L1210 cells were cured when 32 mg/kg or 16 mg/kg of cytarabine in liposomes was given ip every 4 days for a total of three doses. Multivesicular liposomes do prolong intracavitary exposure to cytarabine and are efficacious in this model system.
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D003561:Cytarabine / Q000378:metabolism* / Q000633:toxicity; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D010537:Peritoneum / Q000378:metabolism
D003692:Delayed-Action Preparations; D008081:Liposomes; D003561:Cytarabine; D006851:Hydrochloric Acid