Cyclodextrin MOFs modified dry powder inhalers quadruple bioavailability of luteolin to ameliorate fibrosing interstitial lung disease

Xiaohong Ren; Ting Yang; Kaikai Zhang; Yujie Liu; Caifen Wang; Li Wu; Jiwen Zhang

doi:10.1016/j.ijpharm.2023.123405

Cyclodextrin MOFs modified dry powder inhalers quadruple bioavailability of luteolin to ameliorate fibrosing interstitial lung disease

Int J Pharm. 2023 Oct 15:645:123405. doi: 10.1016/j.ijpharm.2023.123405. Epub 2023 Sep 11.

Authors

Xiaohong Ren¹, Ting Yang², Kaikai Zhang³, Yujie Liu³, Caifen Wang³, Li Wu³, Jiwen Zhang⁴

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China.
³ Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jwzhang@simm.ac.cn.

PMID: 37703957
DOI: 10.1016/j.ijpharm.2023.123405

Abstract

Fibrosing interstitial lung disease (ILD) is a pathological condition that is highly heterogeneous and lethal, and has few effective treatment choices. Other than pirfenidone and nintedanib for the therapy of idiopathic pulmonary fibrosis, no medications are currently licensed for the treatment of ILD. Luteolin is a common flavonoid with multiple biological effects such as anti-inflammation but with poor solubility and absorption. In this study, we loaded luteolin into γ-cyclodextrin metal-organic frameworks (CD-MOFs) to deliver the medicine to the lungs using dry powder inhalers; in vitro pulmonary deposition results showed LUT@CDMOF had a high fine particle fraction (FPF) (59.77 ± 3.48%). LUT@CDMOF effectively inhibited ILD progression in the BLM-induced fibrosing ILD model rats. When compared to oral administration, the inhalation of LUT@CDMOF dry powder in rats showed considerable improvements in absorption and bioavailability, with a t_max of 0.08 h and a high absolute bioavailability (82%) of LUT (The AUC_(0-t) and C_max of inhal. LUT@CDMOF respectively increased about 4.03 times and 9.11 times, when compared with the i.g. LUT group). These studies demonstrate the potent anti-inflammatory activities of LUT@CDMOF. The inhaled LUT@CDMOF might be considered as a promising new strategy in the treatment of fibrosing ILD.

Keywords: Cyclodextrin metal–organic frameworks; Dry powder inhalers; Fibrosing interstitial lung disease; Luteolin.