aclarubicin and Histiocytoma--Benign-Fibrous

The aim of this study was to prepare injectable emulsions of aclacinomycin A (E-ACM) and evaluate its acute toxicity, antitumor effects, and pharmacokinetics. In E-ACM, the surfactants were polyethylene glycol-lipid and cholesterol, and the oil phase was a vitamin E solution of ACM. The particle size distribution and the zeta potential of E-ACM were measured by the laser light dynamic scattering method. The ACM-loading efficiency was measured by using Sephadex G50 column chromatography. The acute toxicity, antitumor effects, and pharmacokinetics of E-ACM were studied in C57BL/6 mice bearing mouse murine histiocytoma M5076 tumors. The average diameter, zeta potential, and ACM-loading efficiency of E-ACM were 123.0 +/- 1.2 nm, - 12.67 +/- 1.35 mv, and 96.3 +/- 0.3% (n = 3), respectively. When stored at 7 degrees C in the dark for 1 year, the average diameter and ACM-loading efficiency of E-ACM changed into 126.3 +/- 2.3 nm and 97.4 +/- 0.8%, respectively, whereas 6.5 +/- 0.2% ACM decomposition was observed (n = 3). The plasma areas under the biodistribution curves (AUC)(0.03-48h) of E-ACM was significantly greater than that of free ACM (F-ACM). The heart, lung, and kidney AUC(0.03-48h) of E-ACM were significantly smaller than those of F-ACM whereas the liver and spleen AUC(0.03-48h) of E-ACM were not significantly different from those of F-ACM. The tumor AUC(0.03-48h) of E-ACM was significantly greater than that of F-ACM. E-ACM had lower acute toxicity and greater potential antitumor effects than F-ACM in M5076 tumor-bearing C57BL/6 mice. E-ACM is a useful tumor-targeting drug delivery system.

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Antioxidants; Cholesterol; Drug Carriers; Emulsions; Histiocytoma, Benign Fibrous; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Mice; Mice, Inbred C57BL; Particle Size; Polyethylene Glycols; Tumor Cells, Cultured; Vitamin E