Design and evaluation of inhalable chitosan-modified poly (DL-lactic-co-glycolic acid) nanocomposite particles

The aim of this study was to investigate two types of chitosan-modified poly (DL-lactic-co-glycolic acid) (PLGA) nanocomposite particles containing salmon calcitonin for pulmonary delivery, which were obtained using spray drying fluidized bed granulation (Agglomaster™) and dry powder coating techniques (Mechanofusion™), respectively. The physicochemical properties, pulmonary distribution, pulmonary clearance rate as well as in vivo hypocalcemia actions of the two types of nanocomposite particles were investigated. As indicated by scanning electron micrographs, soft matrix nanocomposite particles and soft ordered nanocomposite particles were produced by Agglomaster™ and Mechanofusion™, respectively. Both forms of chitosan-modified PLGA nanocomposite particles exhibited a high inhalation efficiency, i.e. more than 50% of the two types of nanocomposite particles could be deposited in the deep lung of male Wistar rats. However, the chitosan-modified PLGA nanocomposite particles designed by Agglomaster™ exhibited superior properties to those obtained by Mechanofusion™ with respect to the redispersibility of fine particles in aqueous liquid, the pulmonary retention time and pharmacological effects. In addition, compared with non-modified PLGA nanocomposite particles, the chitosan-modified PLGA nanocomposite particles obtained by Agglomaster™ exhibited enhanced pulmonary absorption of salmon calcitonin via the lung. The findings in this study suggest that the spray drying fluidized bed granulation technique is superior to the dry powder coating technique for producing chitosan-modified dry powder formulations containing salmon calcitonin for inhalation. This can be attributed to the avoidance of aggregation of chitosan-modified PLGA nanocomposite particles when using Agglomaster™ rather than Mechanofusion™.