Toxicity of free and liposome-encapsulated adriamycin following large volume,short-term intraperitoneal exposure in the rat

The effect of liposome encapsulation on toxicity of the anticancer drug adriamycin (ADR) was studied using large volume intraperitoneal (ip) administration. Concebtrations of 5, 20, and 75 μg/ml of free ADR, ADR encapsulated within lipid vesicles, or ADR in the presence of empty lipid vesicles were tested. The most prominent toxic effect was peritonitis, characterized by accumulation of peritoneal fluid, abdominal adhesions, and histologic evidence of inflammation. Two days after treatment, peritonitis was marginally less with encapsulated than with free ADR. Fourteen days after treatment, peritonitis was generally more severe in the encapsulated 20 μg/ml group than in the free ADR group. At 75 μg/ml the effects of encapsulation on local toxicity were mixed, although the systemic effects were less severe with encapsulation. A generalized hyperlipidemia (Day 14) and elevated LDH levels (Day 2) produced by the highest dose of free ADR were not observed in rats receiving encapsulated ADR. It is concluded that at the concentrations tested, encapsulation appears to offer minimal advantage in reducing local toxicity, but that it may be of benefit in reducing the incidence and severity of systemic toxicity resulting from large volume ip administration of ADR.