Antitumour characteristics of irinotecan-containing microspheres of poly-d,l-lactic acid or poly(d,l-lactic acid-co-glycolic acid) copolymers

Microspheres containing irinotecan showing a gradual drug release were prepared using poly-d,l-lactic acid, poly(d,l-lactic acid-co-glycolic acid) 3/1 copolymer and poly(d,l-lactic acid-co-glycolic acid (1/1)) copolymer by the dry-in-water method. They were named PLA-m PLGA31-m and PLGA11-m, respectively. The drug release rates occurred in the following order, from fastest to slowest: PLGA11-m > PLGA31-m > PLA-m. The effect of microspheres was examined in the intraperitoneal administration with a single dose. In treating mice intraperitoneally bearing P388 leukaemia at a dose of 100 mg irinotecan eq/kg, the effect was raised according to the increase of the drug release rate. At 250 mg irinotecan eq/kg, PLGA11-m showed a high increase in life span, but irinotecan solution gave lethal toxicity. In treating mice bearing sarcomal 80 solid tumour subcutaneously at 250 mg irinotecan eq/kg, tumour growth was suppressed in the following order: PLGA11-m is approximately equal to PLGA31-m > PLA-m, and irinotecan solution gave lethal toxicity. PLGA11-m tended to suppress the tumour growth at 500 mg irinotecan eq/kg; however, body weight loss, being an indicator of a toxic side effect, was observed for mor-e than two weeks.