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Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury

文献类型：期刊论文

作者Luo, Ying2,3; Li, Zeyu3; Wang, Guilan1; Liu, Ergang3; Shen, Huan3; Zhao, Guilong3; Zhao, Ping2; Huang, Yongzhuo2,3,4
刊名AAPS PHARMSCITECH
出版日期2025-09-26
卷号26期号:8页码:17
关键词beta-cyclodextrin acute lung injury dry powder inhalation inclusion cocrystal volatile oil solidification
ISSN号1530-9932
DOI10.1208/s12249-025-03224-2
英文摘要Acute lung injury (ALI) is the major cause of respiratory failure, often triggered by inflammatory responses resulting in disruption of the pulmonary gas-blood barrier. Existing treatments are limited by the poor bioavailability via systemic administration, whereas volatile oils are unsuitable for developing into inhalable formulations. In this study, we developed an inhalable cocrystal of Exocarpium Citri Grandis volatile oil (EVO) using crystallization technology with beta-cyclodextrin (EVO-beta CD), aiming to improve the drug's bioavailability and enhance its therapeutic efficacy for ALI. In vitro studies revealed that EVO-beta CD exhibited no significant cytotoxicity at concentrations of 7.5-120.0 mu g/mL and did not cause hemolysis at concentrations between 3.75-60.0 mu g/mL, suggesting favorable safety profiles. Additionally, EVO and EVO-beta CD significantly reduced the ROS production in LPS pretreated 16HBE cells, highlighting their antioxidant potential. In vivo experiments demonstrated that EVO-beta CD cocrystals were more effective than free EVO in reducing inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) and improving pulmonary edema in LPS-induced acute lung injury in mice. The cocrystal formulation enhanced the release rate of the drug, addressing the challenges of conventional powder inhalants. These findings suggest that EVO-beta CD cocrystals hold promise as a novel therapeutic approach for ALI treatment with enhanced safety and efficacy.Graphical AbstractThe study presents a novel approach for treating acute lung injury (ALI) using a cocrystal formulation of volatile oil from Exocarpium Citri Grandis (EVO) encapsulated by beta-cyclodextrin (EVO-beta CD).
WOS关键词RESPIRATORY-DISTRESS-SYNDROME
资助项目National Key Research and Development Program of China[2022YFE0203060] ; National Key Research and Development Program of China[2024YFA1210204] ; NSFC[82341232] ; NSFC[82404549] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute)[2021B0909050003] ; Zhongshan Municipal Bureau of Science and Technology[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022011] ; Second batch of social welfare and basic research projects of Zhongshan city[2023B2033] ; International Partnership Program of the Chinese Academy of Sciences[083GJHZ2023021GC] ; International Partnership Program of the Chinese Academy of Sciences[083GJHZ2023012FN] ; CAS President's International Fellowship Initiative[2024VBB0004]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001581848600001
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/321561]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Zhao, Guilong; Zhao, Ping; Huang, Yongzhuo
作者单位1.Boai Hosp Zhongshan, Dept Pediat, Zhongshan 528402, Guangdong, Peoples R China
2.Guangdong Pharmaceut Univ, Sch Chem & Chem Engn, Guangzhou 510006, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Luo, Ying,Li, Zeyu,Wang, Guilan,et al. Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury[J]. AAPS PHARMSCITECH,2025,26(8):17.
APA Luo, Ying.,Li, Zeyu.,Wang, Guilan.,Liu, Ergang.,Shen, Huan.,...&Huang, Yongzhuo.(2025).Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury.AAPS PHARMSCITECH,26(8),17.
MLA Luo, Ying,et al."Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury".AAPS PHARMSCITECH 26.8(2025):17.

入库方式： OAI收割

来源：上海药物研究所

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