{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:14:56Z","timestamp":1791976496445,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Toscana, Ministero della Universita\u00e0 e della Ricerca della Repubblica Italiana","award":["I55F20000600007"],"award-info":[{"award-number":["I55F20000600007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: 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. Objectives: This study aims to develop a new formulation suitable for pulmonary administration of ENXM. Methods: A solution for nebulization, based on the complex between ENXM and Hydroxypropyl-\u03b2-Cyclodextrin (HP\u03b2CD) (ENXM\/HP\u03b2CD) is developed. The obtained solution is characterized in terms of aerodynamic distributions and biopharmaceutical features. Results: The evaluation of the aerosol droplets indicates a good bronchi\u2013lung distribution of the drug. Biological evaluations of the air\u2013liquid interface (ALI) in an in vitro lung cell model demonstrates that ENXM\/HP\u03b2CD is capable of a local direct effect, increasing intracellular cyclic adenosine monophosphate (cAMP) levels and protecting from oxidative stress. Conclusions: This study offers a promising advance in the optimization of enoximone delivery to the lungs.<\/jats:p>","DOI":"10.3390\/pharmaceutics16091221","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T03:34:20Z","timestamp":1726716860000},"page":"1221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aerosol of Enoximone\/Hydroxypropyl-\u03b2-Cyclodextrin Inclusion Complex, Biopharmaceutical Evidence for ARDS Applicability"],"prefix":"10.3390","volume":"16","author":[{"given":"Chiara","family":"Migone","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6404-9845","authenticated-orcid":false,"given":"Brunella","family":"Grassiri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1045-005X","authenticated-orcid":false,"given":"Lucia","family":"Vizzoni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"},{"name":"Department of Life Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-840X","authenticated-orcid":false,"given":"Angela","family":"Fabiano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baldassare","family":"Ferro","sequence":"additional","affiliation":[{"name":"Anestesia e Rianimazione, Azienda USL Toscana Nord Ovest, 57124 Livorno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-233X","authenticated-orcid":false,"given":"Ylenia","family":"Zambito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-6400","authenticated-orcid":false,"given":"Anna Maria","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"},{"name":"Centre for Instrument Sharing of University of Pisa (CISUP), 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rizzo, A.N., Aggarwal, N.R., Thompson, B.T., and Schmidt, E.P. 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