title: Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections.
abstract: The influence of vitamin D3 and its metabolites calcifediol (25(OH)D) and calcitriol on immune regulation and inflammation is well described, and raises the question of potential benefit against bacterial infections. In the current study, 25(OH)D was encapsulated in liposomes to enable aerosolisation, and tested for the ability to prevent pulmonary infection by Pseudomonas aeruginosa. Prepared 25(OH)D-loaded liposomes were nanosized and monodisperse, with a negative surface charge and a 25(OH)D entrapment efficiency of approximately 23%. Jet nebulisation of liposomes was seen to yield an aerosol suitable for tracheo-bronchial deposition. Interestingly, 25(OH)D in either liposomes or ethanolic solution had no effect on the release of the proinflammatory cytokine KC from Pseudomonas-infected murine epithelial cells (LA-4); treatment of infected, human bronchial 16-HBE cells with 25(OH)D liposomes however resulted in a significant reduction in bacterial survival. Together with the importance of selecting an application-appropriate in vitro model, the current study illustrates the feasibility and practicality of employing liposomes as a means to achieve 25(OH)D lung deposition. 25(OH)D-loaded liposomes further demonstrated promising effects regarding prevention of Pseudomonas infection in human bronchial epithelial cells.
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany.
authors.forename: Arianna
authors.initials: A
authors.lastname: Castoldi
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology, Critical Care Medicine, Saarland University, Homburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology, Critical Care Medicine, Saarland University, Homburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Niederstraßer
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany; Department of Chemistry & "Cellular and Molecular Bioengineering Research Lab" (CMBRL), University of Calgary, Calgary, Canada; University of Alexandria, Department of Pharmaceutics, Alexandria, Egypt.
authors.forename: Hagar Ibrahim
authors.initials: HI
authors.lastname: Labouta
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany; Department of Pharmaceutics and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Melero
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schneider-Daum
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology, Critical Care Medicine, Saarland University, Homburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany; Department of Pharmacy, Saarland University, Saarbrücken, Germany. Electronic address: Claus-Michael.Lehr@helmholtz-hzi.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000166:cytology; D002112:Calcifediol / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D008081:Liposomes; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D008081:Liposomes; D002112:Calcifediol
keywords: Calcifediol; Cystic fibrosis; Liposome aerosol; Poorly soluble drugs; Pseudomonas aeruginosa; Pulmonary drug delivery