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The objective of this work was to evaluate the acute and subacute toxicity of the injectable alpha compound to Hsd Han: WIST rats. For the acute toxicity assessment, rats were inoculated with doses of 2 000, 1 000, 500, 100, or 10 mg/kg alpha compound intramuscularly. The results of histopathological analysis did not show apparent changes with the doses used. Notably, 2 animals died after treatment with the 2 000 mg/kg dose, and one animal died in the 1 000 mg/kg group. In the subacute toxicity study, neither male nor female rats inoculated with repeated doses of 8, 24, and 40 mg/kg alpha compound showed significant changes in percent body weight (P = 0.5930). Among the females, significant differences were observed for the serum biochemical parameters glucose and cholesterol in the group inoculated with 8 mg/kg compared to the control. The hematocrit values in the 8, 24 and 40 mg/kg groups and the platelet count in the 24 mg/kg group were significantly different (P = 0.0110) among the females compared to the control group. For the male rats, significant differences were found in erythrocyte count and mean corpuscular volume (MCV) in the groups treated with 8 and 40 mg/kg. However, these values are normal according to the literature. The histopathological evaluations did not show apparent changes, so it is concluded that the alpha compound has a wide margin of safety after injection. [ABSTRACT FROM AUTHOR]

Abstract: Casiopeínas® are a new generation of anticancer drugs that have shown great in vitro and in vivo antineoplastic activities. Information about interaction drug-excipient, for developing a based-nanoparticle drug delivery system, has not been investigated yet. In order to elucidate if chitosan (CS) modifies the copper complex due to its interaction with Cu2+ ion, different studies in aqueous media between CS and Casiopeina III-ia (Cas III-ia) were carried out. CS–Cas III-ia mixtures were characterized by viscosity curves, UV–vis, EPR, and in vivo activity against HeLa cell line. Rheological behavior showed a decrease of viscosity when the drug was present due to diminished electrostatic interactions of charged amine group. UV–vis results illustrate that Cas III-ia is not stable at low pH as a result of interaction with acetic acid. However, when chitosan is present at the acidic solution Cas III-ia is stable. These results are supported by EPR studies. Finally, activity of the drug against HeLa cell line was not modified. Therefore, the present work presents evidence that there is no breaking of copper complex due to interaction between CS and Cas III-ia in acidic media. In addition, Cas III-ia maintains both its stability and effectiveness against cancer cell line. [ABSTRACT FROM AUTHOR]