Aerosolization of Lactide/Glycolide Copolymer (PLGA) Nanospheres for Pulmonary Delivery of Peptide-drugs

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Abstract
Lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

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