Toward dosing precision and insulin stability in an artificial pancreas system

A fully implantable artificial pancreas (AP) still represents the holy grail for diabetes treatment. The quest for efficient miniaturized implantable insulin pumps, able to accurately regulate the blood glucose profile and to keep insulin stability, is still persistent. This work describes the design and testing of a microinjection system connected to a variable volume insulin reservoir devised to favor insulin stability during storage. The design, the constitutive materials, and the related fabrication techniques were selected to favor insulin stability by avoiding-or at least limiting-hormone aggregation. We compared substrates made of nylon 6 and Teflon, provided with different surface roughness values due to the employed fabrication procedures (i.e., standard machining and spray deposition). Insulin stability was tested in a worst case condition for 14 days, and pumping system reliability and repeatability in dosing were tested over an entire reservoir emptying cycle. We found that nylon 6 guarantees a higher insulin stability than Teflon and that independent of the material used, larger roughness determines a higher amount of insulin aggregates. A dedicated rotary pump featured by a 1-lL delivery resolution was developed and connected through a proper gear mechanism to a variable volume air-tight insulin reservoir. The microinjection system was also able to operate in a reverse mode to enable the refilling of the implanted reservoir. The developed system represents a fundamental building block toward the development of a fully implantable AP and could be advantageously integrated even in different implantable drug delivery apparatus (e.g., for pain management).