Synthesis of adriamycin-coupled polyglutaraldehyde microspheres and evaluation of their cytostatic activity.

Abstract

Adriamycin was coupled to polyglutaraldehyde microspheres having an average diameter of 4500 .ANG.. The coupled microspheres remained stable during incubation with cells. Full cytostatic activity was observed when the coupled adriamycin was tested with murine leukemia L-1210 cells, CCRF-CEM cells, murine sarcoma S-180 cells, human CCRF-CEM cells, human CCRF-CEM/Vbl 100 cells or human CCRF-CEM/Vbl 500 cells. A 10-fold increase in sensitivity was obtained with drug-resistant human leukemia cell lines. Repeated use of the coupled microspheres in the cytostatic assays did not decrease their activity, indicating that these complexes can be recycled. Coupled adriamycin sufficiently perturbs the plasma membrane to lead to cytostatic activity. This mode of drug delivery provides multiple and repetitious sites for drug-cell interactions. The drug-polymer complexes may overcome those forms of resistance that are the result of decreased drug binding at the cell surface.