Ren Xiaohong, Yang Ting, Zhang Kaikai, Liu Yujie, Wang Caifen, Wu Li, Zhang Jiwen
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.
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.
Int J Pharm. 2023 Oct 15;645:123405. doi: 10.1016/j.ijpharm.2023.123405. Epub 2023 Sep 11.
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 of 0.08 h and a high absolute bioavailability (82%) of LUT (The AUC and C 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.
纤维化间质性肺疾病(ILD)是一种高度异质性且致命的病理状况,有效的治疗选择很少。除了吡非尼酮和尼达尼布用于治疗特发性肺纤维化外,目前尚无药物被批准用于治疗ILD。木犀草素是一种常见的黄酮类化合物,具有多种生物学效应,如抗炎作用,但溶解性和吸收性较差。在本研究中,我们将木犀草素负载到γ-环糊精金属有机框架(CD-MOFs)中,使用干粉吸入器将药物输送到肺部;体外肺部沉积结果显示LUT@CDMOF具有较高的细颗粒分数(FPF)(59.77±3.48%)。LUT@CDMOF有效抑制了博来霉素诱导的纤维化ILD模型大鼠的ILD进展。与口服给药相比,大鼠吸入LUT@CDMOF干粉显示吸收和生物利用度有显著改善,木犀草素的t为0.08小时,绝对生物利用度高(82%)(与口服木犀草素组相比,吸入LUT@CDMOF的AUC和C分别增加了约4.03倍和9.11倍)。这些研究证明了LUT@CDMOF具有强大的抗炎活性。吸入LUT@CDMOF可能被认为是治疗纤维化ILD的一种有前景的新策略。