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

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 γ-cyclodextrin metal-organic frameworks (CD-MOFs) with particle sizes of 1–5 μm to encapsulate l-THP to form inhalable l[email protected] 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[email protected] 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 AUC0–24h and Cmax of l-THP via inhaling SV010-l[email protected] powders increased by approximately 85- and 37-folds, respectively. Moreover, the AUC0–24h 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.