[Studies on lung targeting gelatin microspheres of mitoxantrone].

Lung targeting gelatin microspheres of mitoxantrone (DHAQ) were prepared by a two-step method. The diameter of 87.36% of the DHAQ gelatin microspheres (DHAQ-GMS) was in the range of 5.1 to 25.0 microns. Release of the drug from the DHAQ-GMS in vitro became much slower and its t1/2 was 4 times longer than that of pure DHAQ. The characteristic peak of heat absorption on the differential thermal analysis curve was at 133 degrees C and almost no change was observed after the DHAQ-GMS were stored for 3 months at 37 degrees C (relative humidity 75%). The distribution test in vivo in mice indicated that the lung targeting effect of the DHAQ-GMS was obvious and that the targeting efficiency of the lung compared to other organs and blood increased 3 to 35 times. Kinetic behavior of the drug in mouse lung could be described by one open compartment model, and the average residual time increased by 10 h.

[A study of acute toxicity of mitoxantrone].

Acute toxicity of mitoxantrone (DHAQ) synthetized by Department of Organic Chemistry, School of Pharmacy, WCUMS was studied in mice and dogs. The toxic effects were compared with those of adriamycin (ADR). The LD50 were 6.6 +/- 1.3 and 7.1 +/- 1.6 mg/kg DHAQ, 7.9 +/- 2.1 and 10.7 +/- 2.2 mg/kg ADR (P = 0.95) respectively on observation with a single dose i.v. and i.p., for 21 days in Kunming mice. The toxicity appeared to be delayed with DHAQ and ADR. The earliest death occurred on 4th day after treatment in mice. In the third week still a few died. There were obvious decreases in WBC counts in the peripheral blood of mice receiving either 1-2.5 mg/kg DHAQ or 2.5-5 mg/kg ADR with a single dose i.p.. The WBC count could return to normality after 3 weeks with the withdrawal of the drugs. On electron microscopic examination of myocardial samples from mice 4 days after a single dose of 20 mg/kg DHAQ i.p., mitochondria swelling and vacuoles formation in some cells were shown. Besides the above-mentioned changes, some myocytes exhibited disorientation and loss of myofilaments in the mice which received equivalent dose of ADR. In dogs anaesthetized a temporary falling of blood pressure and slowing of heart rate were observed following 5-10 mg/kg DHAQ i.p.. When a dose of 50-100 mg/kg was given, the blood pressure dropped continuously until death.