In vivo activation and biocompatibility of a MEMS microreservoir drug delivery device

Abstract

Temporal and spatial control over the delivery of therapeutic compounds is an important, fertile, and rapidly advancing field of study in medicine. This work describes the advancement of a new technology of drug delivery from a benchtop prototype releasing tracer molecules to an implantable device for initial animal studies. The improved MEMS (micro-electro-mechanical systems) device was used for the subcutaneous delivery of both tracer molecules (fluorescein and mannitol) and a chemotherapeutic agent (carmustine) in rats. Both temporal and spatial profiles of the tracer molecules were established; only the temporal kinetics of the carmustine were studied. The MEMS drug delivery device is based on a silicon substrate into which microreservoirs are etched. Each reservoir contains an individual dosage of drug and is independently addressable. The microreservoirs are covered with gold membranes which act as anodes. The application of an anodic voltage, in an aqueous solution containing chloride ions, electrochemically transforms gold into gold chloride which is readily soluble in water. This device allows the delivery of both solid and liquid drugs of a wide variety of compositions.

(cont.) It is important to study the biocompatibility of the device activation process as well as that of the component materials since the activation of the MEMS drug delivery device depends on an electrochemical reaction. Other researchers have studied the biological response to gold, silicon, silicon dioxide and silicon nitride; however, few studies of the effect of voltage applications, particularly of gold electrochemistry, have ever been performed. The effects of both electrochemical dissolution of a macroscopic gold film electrode and the repeated electrochemical activation of gold MEMS microelectrodes on the immune response and fibrous capsule formation were observed, as well as the effect of long term implantation on gold electrochemistry.