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Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting.
Puccetti, Matteo; Pariano, Marilena; Renga, Giorgia; Santarelli, Ilaria; D'Onofrio, Fiorella; Bellet, Marina M; Stincardini, Claudia; Bartoli, Andrea; Costantini, Claudio; Romani, Luigina; Ricci, Maurizio; Giovagnoli, Stefano.
Affiliation
  • Puccetti M; Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy.
  • Pariano M; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Renga G; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Santarelli I; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • D'Onofrio F; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Bellet MM; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Stincardini C; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Bartoli A; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Costantini C; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Romani L; Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
  • Ricci M; Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy.
  • Giovagnoli S; Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy.
Cells ; 10(7)2021 06 25.
Article in En | MEDLINE | ID: mdl-34202407
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Delivery Systems / Cystic Fibrosis / Indoles Limits: Animals Language: En Journal: Cells Year: 2021 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Delivery Systems / Cystic Fibrosis / Indoles Limits: Animals Language: En Journal: Cells Year: 2021 Document type: Article Affiliation country: