Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid iso...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/11/4441 |
| _version_ | 1827739347033522176 |
|---|---|
| author | Di Liang Wanmei Wang Guangrui Chen Jian Li Guifang Dou Hui Gan Peng Han Lina Du Ruolan Gu |
| author_facet | Di Liang Wanmei Wang Guangrui Chen Jian Li Guifang Dou Hui Gan Peng Han Lina Du Ruolan Gu |
| author_sort | Di Liang |
| collection | DOAJ |
| description | Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from <i>Stephania cepharantha Hayata</i>. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (D<sub>a</sub>) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model’s establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (<i>p</i> < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI. |
| first_indexed | 2024-03-11T03:01:29Z |
| format | Article |
| id | doaj.art-3eb1e069df984910ba0f22a941b4a830 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T03:01:29Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3eb1e069df984910ba0f22a941b4a8302023-11-18T08:16:42ZengMDPI AGMolecules1420-30492023-05-012811444110.3390/molecules28114441Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung InjuryDi Liang0Wanmei Wang1Guangrui Chen2Jian Li3Guifang Dou4Hui Gan5Peng Han6Lina Du7Ruolan Gu8Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaSevere acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from <i>Stephania cepharantha Hayata</i>. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (D<sub>a</sub>) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model’s establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (<i>p</i> < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.https://www.mdpi.com/1420-3049/28/11/4441cepharanthinepulmonary drug deliveryacute lung injurydry powder inhalers |
| spellingShingle | Di Liang Wanmei Wang Guangrui Chen Jian Li Guifang Dou Hui Gan Peng Han Lina Du Ruolan Gu Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury Molecules cepharanthine pulmonary drug delivery acute lung injury dry powder inhalers |
| title | Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury |
| title_full | Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury |
| title_fullStr | Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury |
| title_full_unstemmed | Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury |
| title_short | Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury |
| title_sort | cepharanthine dry powder inhaler for the treatment of acute lung injury |
| topic | cepharanthine pulmonary drug delivery acute lung injury dry powder inhalers |
| url | https://www.mdpi.com/1420-3049/28/11/4441 |
| work_keys_str_mv | AT diliang cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT wanmeiwang cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT guangruichen cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT jianli cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT guifangdou cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT huigan cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT penghan cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT linadu cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury AT ruolangu cepharanthinedrypowderinhalerforthetreatmentofacutelunginjury |