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

Wenqiang Su, Yinmei Liang, Zhiping Meng, Xuanyu Chen, Manqi Lu, Xingxing Han, Xiaomin Deng, Qichun Zhang, Huaxu Zhu, Tingming Fu

2020Molecular Pharmaceutics66 citationsDOI

Abstract

, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, a 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). A 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, and lung histology 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.

Topics & Concepts

BleomycinPulmonary fibrosisMedicineInhalationTetrandrineHydroxyprolineLungPharmacologyFibrosisPulmonary toxicityPathologyInternal medicineAnesthesiaChemotherapyInterstitial Lung Diseases and Idiopathic Pulmonary FibrosisInhalation and Respiratory Drug DeliveryRespiratory and Cough-Related Research