Drug delivery systems which are configured to retain and then distribute one or more drugs upon an actuating surface and/or balloon for delivery to a tissue region are described herein. The drug delivery system may comprise in one variation a volume of one or more drugs held in a reservoir, e.g., a silo, which may be located proximally of the expandable actuating surface and/or balloon. The one or more drugs may be separated from one another by valves or immiscible fluid barriers for distribution upon the surface, which may be varied in pore distribution, have a coating or covering for facilitating drug distribution, etc.