Migone Chiara, Grassiri Brunella, Vizzoni Lucia, Fabiano Angela, Ferro Baldassare, Zambito Ylenia, Piras Anna Maria
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Department of Life Sciences, University of Siena, 53100 Siena, Italy.
Pharmaceutics. 2024 Sep 19;16(9):1221. doi: 10.3390/pharmaceutics16091221.
Phosphodiesterase (PDE) inhibitors are gaining interest in the context of pulmonary pathologies. In particular, the PDE3 inhibitor enoximone (ENXM) has shown potential relative to the cure of asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Despite its administration via inhalation being planned for use against COVID-19 related ARDS (C-ARDS), presently, no inhalable medicine containing ENXM is available.
This study aims to develop a new formulation suitable for pulmonary administration of ENXM.
A solution for nebulization, based on the complex between ENXM and Hydroxypropyl-β-Cyclodextrin (HPβCD) (ENXM/HPβCD) is developed. The obtained solution is characterized in terms of aerodynamic distributions and biopharmaceutical features.
The evaluation of the aerosol droplets indicates a good bronchi-lung distribution of the drug. Biological evaluations of the air-liquid interface (ALI) in an in vitro lung cell model demonstrates that ENXM/HPβCD is capable of a local direct effect, increasing intracellular cyclic adenosine monophosphate (cAMP) levels and protecting from oxidative stress.
This study offers a promising advance in the optimization of enoximone delivery to the lungs.
磷酸二酯酶（PDE）抑制剂在肺部疾病领域正受到越来越多的关注。特别是，PDE3抑制剂依诺昔酮（ENXM）在治疗哮喘、慢性阻塞性肺疾病（COPD）和急性呼吸窘迫综合征（ARDS）方面已显示出潜力。尽管计划通过吸入方式使用依诺昔酮来治疗与COVID-19相关的ARDS（C-ARDS），但目前尚无含依诺昔酮的可吸入药物。
本研究旨在开发一种适合依诺昔酮肺部给药的新制剂。
研发了一种基于依诺昔酮与羟丙基-β-环糊精（HPβCD）复合物（ENXM/HPβCD）的雾化溶液。对所得溶液进行空气动力学分布和生物药剂学特性表征。
对气溶胶液滴的评估表明药物在支气管-肺部有良好的分布。体外肺细胞模型中对气液界面（ALI）的生物学评估表明，ENXM/HPβCD能够产生局部直接作用，提高细胞内环磷酸腺苷（cAMP）水平并抵御氧化应激。
本研究在优化依诺昔酮肺部给药方面取得了有前景的进展。
