2. Academic Validation
  3. Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections

Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections

  • Eur J Pharm Biopharm. 2017 Sep;118:62-67. doi: 10.1016/j.ejpb.2016.11.026.
Arianna Castoldi 1,  Christian Herr 2,  Julia Niederstraßer 2,  Hagar Ibrahim Labouta 3,  Ana Melero 4,  Sarah Gordon 1,  Nicole Schneider-Daum 1,  Robert Bals 2,  Claus-Michael Lehr 5
Affiliations

Affiliations

  • 1 Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Institute for Infection Research (HZI), Saarbrücken, Germany.
  • 2 Department of Internal Medicine V - Pulmonology, Allergology, Critical Care Medicine, Saarland University, Homburg, Germany.
  • 3 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.
  • 4 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.
  • 5 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.
PMID: 27888144 DOI: 10.1016/j.ejpb.2016.11.026
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.

Keywords

Calcifediol; Cystic fibrosis; Liposome aerosol; Poorly soluble drugs; Pseudomonas aeruginosa; Pulmonary drug delivery.

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