(241b) The Effect of Insulin Loaded PLGA Nano-Composites on the Glycaemia of Beagle Dogs

In a preclinical study, the pharmacological effect of insulin loaded PLGA nano-composites were evaluated with beagle dogs via pulmonary drug delivery. Two types of the nano-composites were prepared for treating type1 diabetes mellitus by spherical crystallization and freeze-drying techniques. One of them was prepared by mixing insulin encapsulated PLGA nano-spheres with sugar alcohol and the other was prepared by mixing insulin encapsulated PLGA nano-spheres with sugar alcohol as well as additional insulin. These nano-composites were designed for easy dispersion in the saline to expose their PLGA nanospheres. The saline containing the nano-composites were intratracheally administrated to beagle dogs with a nebulizer. As a control, the insulin solution was also subcutaneously administered to the beagle dogs. It was found that the nano-composites saline administered intratracheally could have immediate pharmacological effect and prolonged glycaemic efficacy (about 3.5 times longer) on the beagle dogs in comparison to those applying the subcutaneous injection of insulin solution. Furthermore, loading the extra insulin in the nano-composites with sugar alcohol could reduce the dosage amount while achieving the same pharmacological effect as the insulin encapsulated PLGA nanospheres.

Based on the preclinical results, PLGA nano-composites will be formulated for further clinical study.