Mitoxantrone (MXN) has demonstrated therapeutic efficacy in the intraperitoneal treatment of
malignancies. However, severe local toxicity is dose limiting. Therefore, a particulate formulation of MXN, the
drug incorporated in
albumin microspheres, was evaluated concerning tolerability. Survival rates as well as alterations in
body weight, food intake, water intake, urine volume, urine specific gravity, urine
protein content, and complete blood count were observed following single or multiple
intraperitoneal injections of MXN
solution, dispersions containing MXN-loaded
microspheres or unloaded
microspheres, and the injection vehicle to female and male Sprague-Dawley rats. Applied MXN dosage was equivalent to 30 mg/m2 body surface area. Unloaded
microspheres were well tolerated without signs of toxicity. Application of MXN
solution or MXN-loaded
microspheres resulted in similar survival rates (56% 9 weeks after single injection) and in a comparable bone marrow toxicity (mainly leucopenia).
Body weight, food and water intake as well as urine volume were decreased following application of MXN
solution, whereas a progressive gain in weight and no remarkable alterations in nutrition and urine excretion were noted after administration of MXN-loaded and unloaded
microspheres, or of the injection vehicle. In conclusion,
intraperitoneal injection of MXN incorporated in
albumin microspheres exhibits in part less toxicity than conventional treatment.