Development of Functional Dry Powder Formulations for Inhalation, Based on Nanocrystals

Abstract

For application of functional nanocrystals (nPTX) composed of paclitaxel (PTX) and polyethylene glycol derivatives with sustained release and pulmonary retention abilities to inhalation therapy, nPTX-loaded dry powders were newly produced by spray freeze drying (SFD) and their utility as inhaled formulations was investigated in the present study. The nPTX-loaded SFD powders produced with leucine as an excipient were demonstrated to allow reconstruction of nPTX with almost the same particle size distribution, sustained PTX release ability, and anticancer activity as the original ones after their dissolution and to have high aerosol performance for pulmonary delivery through inhalation. Furthermore, the nPTX-loaded SFD powders were clarified to show both more prolonged retention of PTX and milder irritation in the lungs after pulmonary delivery, compared with Taxol, a conventional liquid formulation of PTX. After dissolution of the nPTX-loaded SFD powders on the respiratory epithelium, reconstituted nPTX were found to be rapidly transferred to the lung tissue, followed by prolonged pulmonary retention. In therapeutic evaluation with lung metastasis mice, the nPTX-loaded SFD powders were suggested to exhibit anticancer effects in the lungs after pulmonary delivery. These results strongly indicate that the nPTX-loaded SFD powders are promising to apply to inhalation therapy against lung cancer.