ADRIAMYCIN-LOADED ALBUMIN-HEPARIN CONJUGATE MICROSPHERES FOR INTRAPERITONEAL CHEMOTHERAPY

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) w ere evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspher es after intraperitoneal injection was tested first. 1 day after i.p. administration of empty as well as drug-loaded AHCMS to male Balb/c mi ce, only a moderate increase in i.p. neutrophils was measured. 3 days after injection neutrophil levels were comparable with the controls. N o significant increases in the numbers of other cell types were observ ed, indicating an acute inflammatory response which can be considered to be mild. Antitumour efficacy was tested in an L1210 tumour-bearing mouse model and in a CC531 tumour-bearing rat model. The use of ADR-AH CMS leads to longer survival times of mite and improved tumour growth delay in rats, as compared with untreated controls and free drug treat ed animals. In both animal models higher adriamycin doses were initial ly tolerated if the drug was formulated in microspheres, although long -term adriamycin toxicity effects were evident in all treated groups. Doses and dosage schedules may be optimized to further reduce the toxi c effects of the drug.