INVITRO RELEASE OF BIOLOGICALLY-ACTIVE ADRIAMYCIN BY MAGNETICALLY RESPONSIVE ALBUMIN MICROSPHERES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (10) , 3512-3517
Abstract
The kinetic release of therapeutically active adriamycin from 2 different heat-stabilized preparations of magnetically responsive albumin microspheres (1 .mu.M) was evaluated using a rapid in vitro bioassay-harvesting system. Release products are added to freshly plated monolayers of a malignant Fisher 344 rat fibrosarcoma cell line; the inhibition of [3H]uridine incorporation into trichloroacetic acid-precipitable material (RNA) and whole cells is determined in a 6-h microtiter assay. The latter harvesting technique utilizes semiautomated cell collection using a multiple sample harvester. Standard fluorometric drug analyses are used to quantitate the chemical release rates of adriamycin and related degradation products (aglycones). By altering the temperature of albumin matrix stabilization from 22.degree. to 135.degree., the half-time for the release of therapeutically active drug was varied from 15 min to 9 h. The biological activity of drug products released by the highest temperature (135.degree.) preparation is 78% of that for the native free drug. These in vitro antitumor assays are used to predict the maximal rates of release that could occur at the tissue level under optimal conditions of in vivo targeting.