抄録
This paper describes pharmacological effect of inhaled PLGA nano-composite powder with insulin to beagle dogs as a preclinical test. By a novel particle assembly technique consisting of the spherical crystallization and freeze drying, two types of the nano-composite formulations were prepared for type 1 diabetes mellitus, the first one (preparation (1)) was freeze dried insulin encapsulated PLGA nano-spheres with sugar alcohol; the second one (preparation (2)) was the freeze dried PLGA nano-spheres with sugar alcohol and insulin. These preparations could easily reconstruct the original PLGA nano-spheres in saline, which were intratracheally into the dogs spontaneously breathing. The insulin solution was subcutaneously administered as a reference.
It was found that the PLGA nano-spheres administered intratracheally immediately appeared pharmacological effect and significantly prolonged glycemic effect compared to those of the subcutaneous injection. The pharmacological effects of the preparation (1) and (2) evaluated by the AAC of glycemic profile were approximately 3.5 times higher than the subcutaneous injection.
Furthermore, the preparation (2) could reduce the dosage amount compared with the preparation (1) to obtain the same pharmacologic effect.
Thus, the nano-composite preparations presented here could be formulated to the clinical test as a next stage.
