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

Abstract

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, 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.

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

“…In addition, pulmonary delivery results in minimal systemic exposure and systemic side-effects, allows for high drug concentration in the lung and frequent administration, properties ideal for an anti-cancer drug delivery. Recently, Su et al have reported the formulation of tetrandrine-hydroxy propyl methyl cellulose complex for the treatment of bleomycin-induced pulmonary fibrosis in a murine model and observed excellent accumulation of the complex in the lungs after aerosol delivery [ 12 ]. Other studies report the ability of CDs to enhance pulmonary absorption where relative impermeability of the lungs to several drugs is posing a major obstacle after pulmonary delivery [ 50 ].…”

“…Cyclodextrins are extensively used to improve the water-solubility of poorly water-soluble drugs. CD is reported as a safe excipient via oral, intravenous, and inhalation administration [ 11 , 12 ]. Beta-cyclodextrins (β-CDs) are the most frequently used cyclodextrins in pharmaceutical formulations, due to their ease of availability, cost effectiveness, and ability to readily form inclusion complexes with poorly water-soluble drugs [ 13 , 14 ].…”

Pharmacological hypothesis: TPC2 antagonist tetrandrine as a potential therapeutic agent for COVID‐19

“…While this serum concentration was moderate, average maximal wet lung tissue concentration obtained at postmortem examination following inhalation of the same dose of tetrandrine was over 90 µg/g (~240 µmo/L if lung is treated as 60% water 68 ). 69 Lung concentrations following intravenous administration of 7.5 mg/kg were also relatively high with an average maximal concentration of ~20 µg/g (~53 µmol/L) 69 . In another study investigating the spatiotemporal distribution of tetrandrine in rats using mass spectrometry imaging, 30 mg/kg intravenous administration also resulted in high drug concentrations specifically in the lungs with a peak of ~120 µg/g (~321 µmol/L) 70 …”

Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis: Rationale and therapeutic potential

“…Su et al [ 147 ] prepared an NEB of TET-HP-β-CD, which used tetrandrine to prevent the fibroblasts proliferation, collagen synthesis and reverse fibrosis to treat IPF. Compared to the injection, it can reduce systemic exposure of the drug and toxic and side effects, reduce the number of administrations and increase patient compliance.…”