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Three-Compartment Pharmacokinetics of Inhaled and Injected Sinapine Thiocyanate Manifest Prolonged Retention and Its Therapeutics in Acute Lung Injury

文献类型：期刊论文

作者Li, Zixin4,5,6; Wang, Caifen3,5; Xu, Huipeng5; Wu, Qian3,4,5; Peng, Ningning3,4,5; Zhang, Lu2; Wang, Hui2; Wu, Li5; Li, Zegeng1; Yang, Qinjun2
刊名PHARMACEUTICS
出版日期2025-07-14
卷号17期号:7页码:19
关键词sinapine thiocyanate dry powder inhaler pharmacokinetic acute lung injury MAPK signaling pathway
DOI10.3390/pharmaceutics17070909
通讯作者Yang, Qinjun(yangqinjun@ahtcm.edu.cn) ; Zhang, Jiwen(jwzhang@simm.ac.cn)
英文摘要Background: Acute lung injury (ALI) is driven by inflammatory cascades and reactive oxygen species (ROS) generation, with the progression to severe cases markedly increasing mortality. Sinapine thiocyanate (ST), a bioactive natural compound isolated from Sinapis Semen Albae (SSA), demonstrates both anti-inflammatory and antioxidant pharmacological activities. However, no monotherapeutic formulation of ST has been developed to date. A dry powder inhaler (DPI) enables targeted pulmonary drug delivery with excellent stability profiles and high inhalation efficiency. Methods: ST was purified and prepared as inhalable dry powder particles via an antisolvent crystallization technique. The therapeutic mechanisms of ST against ALI were elucidated by network pharmacology and pharmacokinetic analyses, with the therapeutic efficacy of the ST DPI in ALI mitigation being validated using LPS-induced rat models. Results: The ST DPI showed ideal aerodynamic characteristics. Notably, ST exhibited a three-compartment (triexponential) pharmacokinetic profile following both intravenous tail vein injection and inhalation administration. Furthermore, the inhaled formulation displayed a prolonged systemic residence time, which confers therapeutic advantages for pulmonary disease management. Furthermore, the inhalation administration of ST demonstrated a 2.7-fold increase in AUC compared with oral gavage, with a corresponding enhancement in systemic exposure. The ST DPI formulation demonstrated significant therapeutic efficacy against ALI in rats by downregulating inflammatory cytokines and modulating oxidative stress levels, mechanistically achieved through the MAPK-mediated regulation of cellular apoptosis via a positive feedback loop. Conclusions: The unique triexponential plasma level profiles of an ST DPI provide a promising pharmacokinetics-based therapeutic strategy for ALI, leveraging its marked efficacy in attenuating inflammation, oxidative stress, and pulmonary injury.
WOS关键词FIMASARTAN
资助项目Institute of Health and Medicine, Hefei Comprehensive National Science Center ; National Natural Science Foundation of China[82273863] ; [2023CXMMTCM005]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001539888900001
出版者MDPI
源URL[http://119.78.100.183/handle/2S10ELR8/321141]  
专题中国科学院上海药物研究所
通讯作者Yang, Qinjun; Zhang, Jiwen
作者单位1.Anhui Univ Chinese Med, Affiliated Hosp 1, Dept Resp, Hefei 230031, Peoples R China
2.Anhui Univ Chinese Med, Coll Chinese Med, Hefei 230038, Peoples R China
3.Shenyang Pharmaceut Univ, Coll Pharm, Shenyang 110016, Peoples R China
4.Jiangsu Yungou Pharmaceut Technol Co Ltd, Yangtze Delta Drug Adv Res Inst, Nantong 226133, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201210, Peoples R China
6.Anhui Univ Chinese Med, Coll Pharm, Hefei 230012, Peoples R China
推荐引用方式
GB/T 7714		 Li, Zixin,Wang, Caifen,Xu, Huipeng,et al. Three-Compartment Pharmacokinetics of Inhaled and Injected Sinapine Thiocyanate Manifest Prolonged Retention and Its Therapeutics in Acute Lung Injury[J]. PHARMACEUTICS,2025,17(7):19.
APA Li, Zixin.,Wang, Caifen.,Xu, Huipeng.,Wu, Qian.,Peng, Ningning.,...&Zhang, Jiwen.(2025).Three-Compartment Pharmacokinetics of Inhaled and Injected Sinapine Thiocyanate Manifest Prolonged Retention and Its Therapeutics in Acute Lung Injury.PHARMACEUTICS,17(7),19.
MLA Li, Zixin,et al."Three-Compartment Pharmacokinetics of Inhaled and Injected Sinapine Thiocyanate Manifest Prolonged Retention and Its Therapeutics in Acute Lung Injury".PHARMACEUTICS 17.7(2025):19.

入库方式： OAI收割

来源：上海药物研究所

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