抄録
Pulmonary administration route has been recognized as a potential alternative to intravenous (i.v.) administration for peptide delivery. Nanocomposite particles composed with biodegradable polymeric nanoparticle and sugar alcohol were designed for pulmonary peptide delivery. Aqueous suspension of poly (lactic acid-co-glycolic acid) (PLGA) nanospheres (ca. 250nm in diameter) with insulin was prepared by the emulsion solvent diffusion method in water. The composite particles of resultant nanospheres were prepared by a spray drying fluidized bed granulator (Agglomaster®) . The obtained nanosphere composite particles were the agglomerates of spherical small matrix particles of nanosphere and mannitol (c.a. 4μm in diameter). In vitro inhalation property was evaluated with a cascade impactor. The composite particles showed better inhalation performance than the freeze-dried nanosphere by themselves. In vivo experiment, PLGA nanosphere was rapidly cleared from lung after intratracheal (i.t.) administration. Modification of the nanosphere surface with chitosan prolonged the residence time at the deposited site compared to the unmodified nanospheres. Dry powder inhalation system of chitosan-modified PLGA nanosphere composite with insulin can significantly improve the pharmacological action compared to the solution i.v. or i.t. administered. The relative pharmacological availability to subcutaneous injection was found to be 78%.
