| Popis: |
Pentostatin, a tight binding inhibitor of adenosine deaminase, was used together with N6-(Δ2-isopentenyl)adenosine (IPA) to increase the efficacy of the latter. IPA, although cytotoxic to several types of tumor cells, is unstable due to deamination to inosine by adenosine deaminase. Monolithic polymeric devices were made using segmented polyether polyurethane with both drugs, either individually or together. Drug release data for both drugs gave linear relationships when the amount released per unit area was plotted against the square root of time. Release rates of IPA from the devices were higher than that of pentostatin. The devices were also evaluated for cytotoxic activity of the drugs against cultured L1210 murine leukemic cells. Compared to the intact drugs alone, the polymeric devices enabled a sustained and controlled release of the agents, for a longer period of time. Cell replication was decreased to a marked extent although the initial action was slow. Release of both drugs, when incorporated in the same device, resulted in almost total cell death (⪢ 98%) of an initial population of 11 × 105. Even though the drugs were partially effective individually, the presence of pentostatin together with IPA increased cytotoxic action. The results indicated that sustained release of the enzyme inhibitor together with IPA gave rise to a better delivery system. |
