An Effective Absorption Behavior of Insulin for Diabetic Treatment Following Intranasal Delivery Using Porous Spherical Calcium Carbonate in Monkeys and Healthy Human Volunteers

Porous spherical calcium carbonate (PS-CaCO3), in contrast to regular calcium carbonate (CaCO3), which has a cuboidal particle shape, has a characteristic spherical particle shape with a large number of porous, sliver crystals. The effect of PS-CaCO3 as a drug carrier on intranasal insulin absorption was investigated in cynomolgus monkeys and healthy human volunteers. Each insulin formulation (powder) containing PS-CaCO3 or regular CaCO3 was administered intranasally. Serum insulin and glucose levels after administration were evaluated. The insulin absorption after intranasal administration with each CaCO3 was found to be much more rapid than that after subcutaneous administration. The serum insulin level after intranasal insulin delivery (16 U per monkey) with PS-CaCO3 showed a higher Cmax (403.5 μU/mL) and shorter Tmax (0.167 h) when compared with regular CaCO3. The serum glucose level reduction rate after intranasal delivery using PS-CaCO3 was faster than that of regular CaCO3, reflecting the difference in absorption rates. Following repeated intranasal administrations for 4 weeks in monkeys, no toxicity was observed even with a maximum insulin dose level of 25 U. Furthermore, the intranasal insulin absorption rate with PS-CaCO3 in healthy humans was also observed to be considerably faster than that with regular CaCO3. Effects of PS-CaCO3 on a more effective absorption behavior of insulin were considered to be the result of a greater affinity between the nasal mucosa layer and PS-CaCO3, which is closely related to its structural characteristics. Thus, intranasal insulin delivery using PS-CaCO3 is thought to be a safe and highly available system enabling more effective insulin absorption behavior with the appearance of endogenous postprandial insulin secretion in healthy humans. We believe that our intranasal insulin delivery system enabling a rapid and short-acting pharmacological effect against postprandial hyperglycemia will be more beneficial than pulmonary insulin delivery systems in the treatment of diabetes.