Anti-tumor effect of mitoxantrone-loaded bovine casein microspheres on ehrlich ascites carcinoma in mice

Abstract

Glutaraldehyde cross-linked bovine casein microspheres loaded with the antineoplastic agent mitoxantrone were prepared and in vitro release of the drug into phosphate buffer was examined at 37°C. In the absence of any proteolytic enzymes, the release reached a steady state within a week, releasing only 17-40% of the incorporated drug, depending on the initial payload. In the presence of an enzyme such as protease, however, 100% release was seen in vitro in 2-3 days. The antitumor effect of mitoxantroneloaded microspheres was evaluated in Swiss albino mice bearing Ehrlich ascites carcinoma (EAC) by intraperitoneal injections. The mean survival time of mice receiving 1 mg of mitoxantrone as free drug was 4.6 ± 0.67 days as opposed 37.7 ± 2.9 days for mice receiving equivalent amount of drug encapsulated in microspheres (p < 001). The percent T/C ratio of the animals receiving treatment via microsphere modality was 219.2, as opposed to 26.7 for the group receiving therapy using free drug. There was no significant increase in the body weight of animals receiving the drug-loaded microspheres. It is demonstrated that sustained delivery of mitoxantrone intraperitoneally using casein microspheres would be a promising approach in the treatment of EAC.