ABSTRACT
This chapter illustrates how microspheres can be used to restrict drug action to the plasma membrane resulting in a novel mechanism of cytotoxicity. The chemical and physical properties of microspheres utilized for membrane targeting can vary significantly as long as they are biocompatible and can be covalently linked with the chosen drug. The locations of the microspheres were categorized as extracellular, surface-bound, cytoplasmic, or nuclear. The ability of Adriamycin (Adr) microspheres to bind to and kill tumor cells in vitro without Adr detaching from the microspheres and without the microspheres being internalized demonstrated that the cytotoxic effect occurs at the level of the cell membrane upon contact with drug microspheres. Cytostatic assays were used to determine the growth-inhibiting effects of Adr-Pgl on sensitive and Adr-resistant cell lines. As a measure of cytotoxicity, the colony-forming ability of individual cells was assayed in soft agarose by Dr. Kathy Rogers, using a modification of the procedure of L. Macpherson and M. K. Patterson.
