Inhalative administration of insulin using a new bubble jet atomization device.

OBJECTIVES: In this study, we attempted to perform inhalative administration of insulin using a new "bubble jet" atomization device based on ink jet printing technology and developed by Canon Inc. The aim of this study was to confirm the usefulness of the new device for achieving a hypoglycemic effect by insulin inhalation in normal rats. METHODS: Inhaled insulin (15 U/kg) or a control solution without insulin was administrated to each Wistar rat intratracheally using the bubble-jet atomization device. Blood glucose concentrations were measured at 0, 10, 20, 30, 60, 90 and 120 min after administration of insulin or control solution. RESULTS: The blood glucose concentrations in the inhaled insulin group were 63 +/- 10 mg/dl (20 min), 43 +/- 8 mg/dl (60 min) and 35 +/- 9 mg/dl (120 min), while those in the control solution group were 80 +/- 9 mg/dl (p = 0.016), 75 +/- 10 mg/dl (p < 0.001) and 85 +/- 27 mg/dl (p < 0.001). The blood glucose concentrations after administration of inhaled insulin were significantly lower than those after administration of control solution at all time points (p < 0.05) except 0 and 10 min. CONCLUSIONS: We confirmed the hypoglycemic effect of inhaled insulin using the new bubble jet atomization device. These results proved that the new device could atomize insulin while maintaining its bioactivity.

Novel hormonal delivery method using the ink-jet technology: application to pulmonary insulin therapies.

BACKGROUND: A device developed based on ink-jet printer technology can precisely control the size and volume of droplets ejected. Here, we evaluated the application of this technology to the pulmonary administration of insulin mist as a therapeutic measure for diabetes. METHODS: Insulin ejected from the ink-jet device was initially characterized by high-performance liquid chromatography (HPLC) and mass spectrometry. Its effects on D-glucose uptake rate by L6 cells were then investigated. Next, different insulin solutions (with or without additives or ink-jet processing) were subcutaneously administered, and their pharmacodynamic features were evaluated. Finally, decreases in plasma glucose level in rats were examined after ventilator-assisted pulmonary administration of insulin mist. RESULTS: Neither the HPLC nor the mass spectrometry profile of insulin was altered by the ink-jet process. The D-glucose uptake rate by L6 cells that received the recovered aerosolized insulin solution was similar to that of cells treated with control insulin, at 107%. Neither the addition of additives nor the ink-jet process used for insulin aerosolization impaired the plasma glucose-lowering action of subcutaneously injected insulin. Similarly, the efficacy of pulmonary insulin administration was not affected by the additives or the ink-jet process. Plasma glucose levels showed a trend towards decreasing after ventilator-assisted pulmonary administration of insulin mist. Plasma insulin level increased 30 min after the inhalation. CONCLUSIONS: The ink-jet process did not affect the quality or biological activity of insulin, suggesting the potential use of the ink-jet device for insulin inhalation therapy for diabetes.