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Highly efficient pulmonary delivery of levo-tetrahydropalmatine using gamma-cyclodextrin metal-organic framework as a drug delivery platform

文献类型：期刊论文

作者Nie, Qin1,2; Wang, Caifen1,2; Xu, Huipeng2,3; Mittal, Priyanka2,3; Naeem, Abid4; Zhou, Panpan1,2; Li, Haiyan2; Zhang, Yu1,2; Guo, Tao2; Sun, Lixin1
刊名JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
出版日期2023-04-01
卷号82页码:12
关键词Levo-tetrahydropalmatine Pulmonary delivery gamma-Cyclodextrin metal-organic frameworks Dry powder inhaler Bioavailability
ISSN号1773-2247
DOI10.1016/j.jddst.2023.104296
通讯作者Sun, Lixin(slx04@163.com) ; Zhang, Jiwen(jwzhang@simm.ac.cn)
英文摘要Levo-tetrahydropalmatine (l-THP), an active ingredient used to treat lung injury, shows limited therapeutic potential due to its poor solubility and low absorption. This study uses gamma-cyclodextrin metal-organic frameworks (CD-MOFs) with particle sizes of 1-5 mu m to encapsulate l-THP to form inhalable l-THP@CD-MOF powders that simultaneously improve the solubility and facilitate pulmonary delivery. Characterization analysis and in vitro deposition of the powders were carried out using scanning electron microscopy (SEM), powder X-ray diffractometry (PXRD), next-generation impactor (NGI), etc. The perfect aerosolization was achieved with a fine particle fraction (FPF) of 37.25 +/- 2.80% when the powders were formulated with lactose (SV010). The results showed that l-THP@CD-MOF particles were eliminated much faster than l-THP in rat liver microsomes (RLuM) and rat lung microsomes (RLiM) medium. Compared to the oral administration in vivo, the AUC(0-24h) and C-max of l-THP via inhaling SV010-l-THP@CD-MOF powders increased by approximately 85-and 37-folds, respectively. Moreover, the AUC(0-24h) of its metabolites, including L-isocorypalmine (L-ICP) and L-corypalmine (L-CP) were also increased apparently. In conclusion, the dry powder inhaler (DPI) of l-THP was delivered efficiently to the lungs and significantly improved the bioavailability of l-THP and its active metabolites in vitro and in vivo, which may make l-THP a promising treatment for a wide range of respiratory diseases.
WOS关键词POWDER INHALER FORMULATION ; CD-MOF ; RAT ; PHARMACOKINETICS ; PERFORMANCE ; PLASMA ; ENANTIOMERS ; METABOLISM ; CORYDALINE ; INHALATION
资助项目National Key R & D Program of China[2020YFE0201700] ; Opening Project of Zhejiang Provincial First -rate Subject ; Opening Project of Zhejiang Provincial First-rate Subject (Chinese Traditional Medicine) from Zhejiang Chinese Medical University[Ya2017006]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000993484500001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/306671]  
专题中国科学院上海药物研究所
通讯作者Sun, Lixin; Zhang, Jiwen
作者单位1.Shenyang Pharmaceut Univ, Sch Pharm, Dept Pharmaceut Anal, 103 Wenhua Rd, Shenyang 110016, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, 501 Haike Rd, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
4.Jiangxi Univ Chinese Med, Key Lab Modern Preparat TCM, Minist Educ, 1688 Meiling Rd, Nanchang 330004, Peoples R China
5.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, 2 Tiantan Xili, Beijing 100050, Peoples R China
推荐引用方式
GB/T 7714		 Nie, Qin,Wang, Caifen,Xu, Huipeng,et al. Highly efficient pulmonary delivery of levo-tetrahydropalmatine using gamma-cyclodextrin metal-organic framework as a drug delivery platform[J]. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY,2023,82:12.
APA Nie, Qin.,Wang, Caifen.,Xu, Huipeng.,Mittal, Priyanka.,Naeem, Abid.,...&Zhang, Jiwen.(2023).Highly efficient pulmonary delivery of levo-tetrahydropalmatine using gamma-cyclodextrin metal-organic framework as a drug delivery platform.JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY,82,12.
MLA Nie, Qin,et al."Highly efficient pulmonary delivery of levo-tetrahydropalmatine using gamma-cyclodextrin metal-organic framework as a drug delivery platform".JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY 82(2023):12.

入库方式： OAI收割

来源：上海药物研究所

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