Liang Di, Lv Zihan, Meng Zhiyun, Liu Shuchen, Gan Hui, Han Peng, Wu Zhuona, Du Lina, Gu Ruolan, Dou Guifang
Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Sci Rep. 2025 Jul 1;15(1):20989. doi: 10.1038/s41598-025-04167-1.
The symptoms of coronavirus disease 2019 (COVID-19) range from severe lung disease to milder manifestations, such as cough and throat irritation. As a bisbenzylisoquinoline alkaloid, cepharanthine (CEP) has various pharmacological properties, such as antifibrotic, anti-inflammatory, antioxidant, and antiviral effects. However, its poor solubility and low bioavailability hinder subsequent drug development. Inclusion complex technology is a well-established drug delivery method that improves drug bioavailability. Therefore, in our study, we encapsulated CEP with β-cyclodextrin and formulated it into oral tablets. Oral tablets can be absorbed through sublingual and buccal mucosa, improving CEP bioavailability, facilitating convenient dosing, and thereby enhancing its therapeutic efficacy. The cepharanthine-β-cyclodextrin (CEP-β-CD) inclusion complex was prepared using the co-grinding method. It was characterized using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry to assess its physicochemical properties. Subsequently, the quality of the CEP-β-CD oral tablets was evaluated according to the relevant requirements of the 2020 edition of the Chinese Pharmacopoeia. Furthermore, the pharmacokinetic characteristics of the oral tablets were assessed in beagles. Finally, the anti-inflammatory effects of the CEP-β-CD oral tablets were evaluated in alveolar macrophage MH-S cells and a mouse pneumonia model. Our results suggest that the formulation of the CEP-β-CD inclusion complex into oral tablets is a promising preventive and therapeutic approach for lung injury caused by COVID-19.
2019冠状病毒病（COVID-19）的症状范围从严重的肺部疾病到较轻的表现，如咳嗽和咽喉刺激。千金藤素（CEP）作为一种双苄基异喹啉生物碱，具有多种药理特性，如抗纤维化、抗炎、抗氧化和抗病毒作用。然而，其溶解度差和生物利用度低阻碍了后续的药物开发。包合物技术是一种成熟的药物递送方法，可提高药物的生物利用度。因此，在我们的研究中，我们用β-环糊精包封CEP并将其制成口服片剂。口服片剂可通过舌下和颊黏膜吸收，提高CEP的生物利用度，便于给药，从而增强其治疗效果。采用共研磨法制备了千金藤素-β-环糊精（CEP-β-CD）包合物。使用扫描电子显微镜、X射线衍射、傅里叶变换红外光谱和差示扫描量热法对其进行表征，以评估其理化性质。随后，根据《中国药典》2020年版的相关要求对CEP-β-CD口服片剂的质量进行了评价。此外，在比格犬中评估了口服片剂的药代动力学特征。最后，在肺泡巨噬细胞MH-S细胞和小鼠肺炎模型中评估了CEP-β-CD口服片剂的抗炎作用。我们的结果表明，将CEP-β-CD包合物制成口服片剂是一种有前景的预防和治疗COVID-19所致肺损伤的方法。
