Highly efficient pulmonary delivery of levo-tetrahydropalmatine using -cyclodextrin metal-organic framework as a drug delivery platform
Journal of Drug Delivery Science and Technology(2023)
Abstract
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.
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Key words
Levo-tetrahydropalmatine,Pulmonary delivery,gamma-Cyclodextrin metal-organic frameworks,Dry powder inhaler,Bioavailability
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