Selective targeting of magnetic albumin microspheres containing low-dose doxorubicin: total remission in Yoshida sarcoma-bearing rats

Abstract

Magnetically responsive albumin microspheres containing doxorubicin hydrochloride were selectively localized in Yoshida sarcoma tumors. Tumors were implanted subcutaneously in the tail of Holtzman rats and allowed to grow to at least 200 mm2 size before initiation of experimental treatment. Drug-bearing microspheres at a dose level of either 0.5 or 2.5 mg/kg were infused proximal to the tumor via the ventral caudal artery. A bipolar permanent magnet was placed adjacent to the tumor during the infusion to effect localization. Control animals were treated with free doxorubicin infused intra-arterially at 5.0 mg/kg or 0.5 mg/kg. In other test groups animals received placebo microspheres localized in the tumor via influence of the external magnetic field, or drug-containing microspheres were infused without utilization of the magnet to effect localization. Of the 22 animals receiving magnetically localized doxorubicin microspheres 17 had total histological remission of the tumor. The remaining animals demonstrated marked tumor regression representing as much as 500-600 mm2 decrease in tumor size. While no deaths or metastases occurred in the groups receiving localized drug, animals treated with free doxorubicin, placebo microspheres or non-localized doxorubicin microspheres exhibited a significant increase in tumor size with metastases and subsequent death in 90-100% of the animals. No significant differences were noted in tumor regression/remission data between the 0.5 and 2.5 mg/kg dose levels of magnetically localized doxorubicin spheres. These results represent a significant advance in targeted chemotherapy in that 77% of the animals in the magnetically localized doxorubicin microsphere treatment groups exhibited total remission after only one regimen of drug therapy.