Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting.
Inflammation plays a major role in the pathophysiology of cystic fibrosis (CF), a multisystem disease. Anti-inflammatory therapies are, therefore, of interest in CF, provided that the inhibition of inflammation does not compromise the ability to fight pathogens. Here, we assess whether indole-3-aldehyde (3-IAld), a ligand of the aryl hydrocarbon receptor (AhR), may encompass such an activity. We resorted to biopharmaceutical technologies in order to deliver 3-IAld directly into the lung, via dry powder inhalation, or into the gut, via enteric microparticles, in murine models of CF infection and inflammation. We found the site-specific delivery of 3-IAld to be an efficient strategy to restore immune and microbial homeostasis in CF organs, and mitigate lung and gut inflammatory pathology in response to fungal infections, in the relative absence of local and systemic inflammatory toxicity. Thus, enhanced delivery to target organs of AhR agonists, such as 3-IAld, may pave the way for the development of safe and effective anti-inflammatory agents in CF.
['Puccetti|Matteo|M|0000-0003-3007-0475', 'Pariano|Marilena|M|', 'Renga|Giorgia|G|0000-0002-9762-6493', 'Santarelli|Ilaria|I|', "D'Onofrio|Fiorella|F|", 'Bellet|Marina M|MM|', 'Stincardini|Claudia|C|', 'Bartoli|Andrea|A|', 'Costantini|Claudio|C|0000-0002-1433-7830', 'Romani|Luigina|L|', 'Ricci|Maurizio|M|0000-0002-3373-9771', 'Giovagnoli|Stefano|S|0000-0001-5043-7233']
D000280:Administration, Inhalation D000336:Aerosols D000818:Animals D003550:Cystic Fibrosis D019005:Cystic Fibrosis Transmembrane Conductance Regulator D004195:Disease Models, Animal D016503:Drug Delivery Systems D041981:Gastrointestinal Tract D007211:Indoles D008024:Ligands D008168:Lung D008810:Mice, Inbred C57BL D018336:Receptors, Aryl Hydrocarbon
drug delivery cystic fibrosis inflammation 3-IAld aryl hydrocarbon receptor