{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:22:51Z","timestamp":1785248571205,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Municipal Natural Science Foundation","award":["20SW AQK22"],"award-info":[{"award-number":["20SW AQK22"]}]},{"name":"Beijing Municipal Natural Science Foundation","award":["145AHQ080014008X-12-02"],"award-info":[{"award-number":["145AHQ080014008X-12-02"]}]},{"name":"Chinese Biosafety Construction Project","award":["20SW AQK22"],"award-info":[{"award-number":["20SW AQK22"]}]},{"name":"Chinese Biosafety Construction Project","award":["145AHQ080014008X-12-02"],"award-info":[{"award-number":["145AHQ080014008X-12-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 Stephania cepharantha Hayata. 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 (Da) of the DPIs was 3.2 \u03bcm, 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\u2019s 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-\u03b1, IL-6 and total protein) in their lungs (p &lt; 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.<\/jats:p>","DOI":"10.3390\/molecules28114441","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T02:57:10Z","timestamp":1685501830000},"page":"4441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8993-0436","authenticated-orcid":false,"given":"Di","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7281-6530","authenticated-orcid":false,"given":"Guangrui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-5974","authenticated-orcid":false,"given":"Lina","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/s41419-020-03034-3","article-title":"Mesenchymal Stem Cells Reverse EMT Process through Blocking the Activation of NF-\u039aB and Hedgehog Pathways in LPS-Induced Acute Lung Injury","volume":"11","author":"Xiao","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0140-6736(07)60604-7","article-title":"Acute Lung Injury and the Acute Respiratory Distress Syndrome: A Clinical Review","volume":"369","author":"Wheeler","year":"2007","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.ejcb.2011.11.004","article-title":"Models and Mechanisms of Acute Lung Injury Caused by Direct Insults","volume":"91","author":"Reiss","year":"2012","journal-title":"Eur. 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