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Abstract: Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using MechanofusionTM to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the MechanofusionTM technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs. [Copyright &y& Elsevier]

The objective of the present research is to develop a new particulate preparation process for dry powder inhalation by which peptide-loaded poly(DL-lactic-co-glycolic acid) nanospheres are granulated with sugar alcohol (mannitol, around 4 μm in diameter). A spray-drying fluidized bed granulator was used to form soft matrix composite granules. A nanosphere suspension can be readily obtained by dispersing the composite granules in distilled water. The composite granules showed inhalation performance superior to that of freeze-dried nanosphere powder. More than 50% of composite granules were delivered to the bronchioles and alveoli of a rat. The composite granules of insulin-loaded nanosphere have a strong and prolonged pharmacological effect compared to the inhalation of insulin solution. [ABSTRACT FROM AUTHOR]