Antitumor Effects and Pharmacokinetics of Carried by Injectable Emulsions Composed Cholesterol, and PEG-Lipid

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'C in the dark for I 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 (AUOo 03-48h of E-ACM was siguificantly greater than that of free ACM (F-ACM). The heart, Iung, and kidney AUCo,03-48h of E-ACM were siguificantly smaller than those of F-ACM whereas the liver and spleen AUCO 03-48h of E-ACM were not significantly different from those of F-ACM. The tumor AUCo.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. C 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 1 1281 134, 2002