Bioavailability Enhancement of Cepharanthine via Pulmonary Administration in Rats and Its Therapeutic Potential for Pulmonary Fibrosis Associated with COVID-19 Infection

Molecules

Hui Gan¹  Peng Han¹  Jian Li¹  Zhuona Wu¹  Guangrui Chen¹  Taoyun Liu¹  Fanjun Wang¹  Zhiyun Meng¹  Xiaoxia Zhu¹  Guifang Dou¹  Ruolan Gu¹ 

[1] Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China;

关键词: cepharanthine;    COVID-19;    pulmonary delivery;    anti-fibrosis;    UPLC-MS/MS;    bioavailability;   

DOI  :  10.3390/molecules27092745

来源: DOAJ

【 摘 要 】

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-β1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.

【 授权许可】

Unknown