Co-achievement of enhanced absorption and elongated retention of insoluble drug in lungs for inhalation therapy of pulmonary fibrosis

The unique composite particles consisting of γ-cyclodextrin metal-organic framework (MOF) (0.5–3 μm of geometric particle size) and 18 β-Glycyrrhetinic acid (GA) were developed as dry powder inhaler (DPI) to alleviate idiopathic lung fibrosis (IPF), which possessed the property of biphasic release in vivo and vitro. In vitro release, the burst release of almost 55% emerged before 2 min and the continued release maintained till 120 h. This specifical phenomenon might be attributed to the structure of MOF containing a pair of γ-CD and cavity. Compared to GA raw material group, the AUC0-t and Cmax of GA@MOF inhalation were enhanced about 3.8 times and 21.4 times, respectively. Furthermore, the absorption time prolonged by 8 h which elongated retention of GA in lungs. Evident by the 92% deposition of GA in the lung based on its biodistribution result, it made sense to expect a locally direct effect on IPF via inhalation