Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury

Abstract 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, antioxi...

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Main Authors: Di Liang, Zihan Lv, Zhiyun Meng, Shuchen Liu, Hui Gan, Peng Han, Zhuona Wu, Lina Du, Ruolan Gu, Guifang Dou
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04167-1
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author Di Liang
Zihan Lv
Zhiyun Meng
Shuchen Liu
Hui Gan
Peng Han
Zhuona Wu
Lina Du
Ruolan Gu
Guifang Dou
author_facet Di Liang
Zihan Lv
Zhiyun Meng
Shuchen Liu
Hui Gan
Peng Han
Zhuona Wu
Lina Du
Ruolan Gu
Guifang Dou
author_sort Di Liang
collection DOAJ
description Abstract 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.
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spelling doaj-art-a15006a652b04ac8b3e2f421271439cd2025-08-20T03:37:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-04167-1Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injuryDi Liang0Zihan Lv1Zhiyun Meng2Shuchen Liu3Hui Gan4Peng Han5Zhuona Wu6Lina Du7Ruolan Gu8Guifang Dou9Beijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineAbstract 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.https://doi.org/10.1038/s41598-025-04167-1CepharanthineInclusion complexOral tabletAnti-inflammatory
spellingShingle Di Liang
Zihan Lv
Zhiyun Meng
Shuchen Liu
Hui Gan
Peng Han
Zhuona Wu
Lina Du
Ruolan Gu
Guifang Dou
Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury
Scientific Reports
Cepharanthine
Inclusion complex
Oral tablet
Anti-inflammatory
title Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury
title_full Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury
title_fullStr Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury
title_full_unstemmed Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury
title_short Development and evaluation of cepharanthine-β-cyclodextrin inclusion complex oral tablets for prevention and treatment of COVID-19 lung injury
title_sort development and evaluation of cepharanthine β cyclodextrin inclusion complex oral tablets for prevention and treatment of covid 19 lung injury
topic Cepharanthine
Inclusion complex
Oral tablet
Anti-inflammatory
url https://doi.org/10.1038/s41598-025-04167-1
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