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In Vitro Release of Biologically Active Adriamycin by Magnetically Responsive Albumin Microspheres¹

Department of Pathology and the Northwestern University Cancer Center, Northwestern University Medical and Dental School, Chicago, Illinois 60611 [K.J.W., A.E.S.], and Department of Pathology, University of Texas Health Science Center, Dallas, Texas 75235 [D.F.R.]

The kinetic release of therapeutically active Adriamycin from two different heat-stabilized preparations of magnetically responsive albumin microspheres (1 µm) has been 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, and the inhibition of [³H]uridine incorporation into trichloroacetic acid-precipitable material (RNA) and whole cells is determined in a 6-hr 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 to 135°, the half-time for the release of therapeutically active drug has been varied from 15 min to 9 hr. The biological activity of drug products released by the highest temperature (135°) 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.

¹ A preliminary report of this work was presented at the 69th Annual Meeting of the American Association for Cancer Research, Inc., Washington, D. C., April 1978 (14). This work was supported by the Department of Pathology, Northwestern University Medical and Dental Schools; the Northwestern University Cancer Center; and Grant R01 CA26031 from the National Cancer Institute.

² Present address: Department of Pathology, Duke University Medical Center, Durham, N. C., 27710. To whom requests for reprints should be addressed.

³ Present address: Department of Obstetrics and Gynecology, California College of Medicine, University of California, Irvine, Calif., 92717.

⁴ Present address: Department of Pathology, University of Texas Health Science Center, Dallas, Texas 75235.

Received 12/17/79. Accepted 7/ 3/80.

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