Antitumor effect of implanted ethylene-vinyl alcohol copolymer matrices containing anticancer agents on Ehrlich ascites carcinoma and P388 leukemia in mice.

Abstract

Ethylene-vinyl alcohol (EVAI) copolymer was evaluated as a vehicle for controlled or sustained release of 5-fluorouracil (5-FU) and adriamycin. The variation of initial drug concentration and, to an even greater extent, the variation in comonomer ratio affected the drug release rate as well as the cumulative amount of the drug released. An increase in the ethylene content of the EVAI copolymer decreased drug release. It appears that EVAI copolymer can be used as a membrane for controlling the release of 5-FU or adriamycin. The antitumor activity of EVAI copolymer matrices containing these anticancer agents was evaluated against Ehrlich ascites carcinoma (EAC) in mice on the basis of changes in body weight and animal survival data. Tumor cell injections were performed on day 0 and matrix implantations on day 3, both intraperitoneally. The suppressive effect of matrices containing anticancer agents on the increase in body weight was higher than that of the free drugs. A prolongation of the life span of tumor-bearing mice following implantation of therapeutic matrices was also noted. Implantation of the EVAI copolymer matrix containing an anticancer agent was less effective against the P388 leukemia than the EAC. These results suggest that EVAI copolymer matrices containing anticancer agents may be effective in cancer chemotherapy. Matrices composed of EVAI copolymer could be useful vehicles for implanted delivery systems for anticancer agents.