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

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.     

One-dimensional coordination polymers of praseodymium(III)–vanadium(V) complexes with pyridine-2,6-dicarboxylic acid

This paper represents the hydrothermal synthesis of new isomorphous lanthanide–vanadium complexes with one-dimensional coordination polymers: [Pr₂(VO₂)₂(dipic)₄(H₂O)₉] · nH₂O with dipic = pyridine-2,6-dicarboxylic acid and n = 7.75. The structure determination shows a unique one-dimensional structure in which three types of chains run along the c-axis: the chain of positively charged praseodymium complexes bridged by a dipic ligand ([Pr(dipic)(H₂O)₅]⁺), the chain of negatively charged, stacked vanadium complexes ([VO₂(dipic)]⁻), and the chain of neutral praseodymium complexes with a bridged dipic ligand and a coordinating dipic ligand ([Pr(dipic)[VO₂(dipic)](H₂O)₄]). Such one-dimensional chains provide open channels which can accommodate water molecules. Not only accommodated water molecules but also ones coordinated to praseodymium ions were easily removed and absorbed upon heating at 200 °C and exposure of humidity at room temperature, respectively.