Enhancement of the antitumor activity of N6-(delta 2-isopentenyl)adenosine against cultured L-1210 leukemia cells by pentostatin using a polymeric delivery system.

The adenosine deaminase inhibitor pentostatin (I), recently shown to be effective in the treatment of several types of acute and chronic human leukemias, was impregnated in a silicone polymer monolithic disk device for release in vitro in the presence of the antitumor nucleoside N6-(delta 2-isopentenyl)adenosine (II) against mouse L-1210 lymphocytic leukemia cells. Although I is ineffective alone against L-1210 cells, controlled release from the polymeric delivery matrix potentiates the antiproliferative effects of II during the midlog phase of growth (48 hr). Cytotoxicity is prolonged, leading to total cell death during the stationary phase of growth (96 hr). The present study suggests that polymeric delivery systems be used for controlled release of oncologic agents, alone or in combination with inhibitors, especially where liability is a concern.