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Inhalation of Tetrandrine- hydroxypropyl-β-cyclodextrin Inclusion Complexes for Pulmonary Fibrosis Treatment.

Pulmonary fibrosis (PF) is a kind of interstitial lung disease with the features of progressive and often fatal dyspnea. Tetrandrine (TET) is the major active constituent of Chinese herbal Stephania tetrandra S. Moore, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, tetrandrine-hydroxypropyl-β-cyclodextrin inclusion compound (TET-HP-β-CD) was developed for the treatment of pulmonary fibrosis via inhalation administration. TET-HP-β-CD was prepared by the freeze-drying method and identified using the cascade impactor, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectrum (FT-IR). Bleomycin-induced pulmonary fibrosis rat model was used to assess the effects of inhaled TET and TET- HP-β-CD. Animal survival, hydroxyproline content in the lungs, lung histology and protein expression were detected. The results showed that inhalation of TET-HP-β-CD alleviated inflammation and fibrosis, limited the accumulation of hydroxyproline in the lungs, regulated protein expression in PF development and improved postoperative survival. Moreover, nebulized delivery of TET-HP-β-CD accumulated chiefly in the lungs and limited systemic distribution compared with intravenous administration. The present results indicated that inhalation of TET-HP-β-CD is an attractive candidate for the treatment of pulmonary fibrosis.