Supplemental insulin delivery from an implanted reservoir activated by external compression

An implant made of insulin in palmitic acid provides a basal dose sufficient to reduce hyperglycemia for 42 +/- 12 days in rats with induced diabetes. For preprandial dose supplements another arrangement is required. In this study a device consisting of a reservoir is assembled by attaching a 1 cm diameter foam ring to a 5 mm diameter piece of the same material. A 6 mg piece of compressed insulin is inserted into a cut between the ring and the attachment, along with 2 mg tetracycline to hinder microbial growth. The assembly is then enclosed between two membranes and an annular external wall. The top membrane is pierced once, and the device is tested by implantation under the abdominal skin of diabetic rats. Serous fluid will enter the interior through the orifice and leach the solid insulin that does not leak out. Daily sidewise compression over the skinfold of the unanesthetized animal indicated that the insulin supply lasted for 24 +/- 4 days. The blood glucose was consistently maintained at 3.4 +/- 1.1 mmol/L for 6-8 hr each day. After depletion the device can be refilled percutaneously by injecting insulin suspended in phosphate-buffered saline.