6533b7d9fe1ef96bd126b950

RESEARCH PRODUCT

Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections.

Claus-michael LehrSarah GordonRobert BalsJulia NiederstraßerArianna CastoldiHagar I. LaboutaNicole Schneider-daumChristian HerrAna Melero

subject

0301 basic medicineVitaminRMCalcitriolCystic FibrosisPharmaceutical ScienceInflammationBronchiBiologyPharmacologymedicine.disease_causeMicrobiologyProinflammatory cytokineCell Line03 medical and health scienceschemistry.chemical_compoundMice0302 clinical medicinePseudomonas infectionAdministration InhalationmedicineAnimalsHumansImmunologic FactorsPseudomonas InfectionsRespiratory Tract InfectionsCalcifediolLiposomePseudomonas aeruginosaEpithelial CellsGeneral Medicinemedicine.disease030104 developmental biology030228 respiratory systemchemistryLiposomesPseudomonas aeruginosaCytokinesNanoparticlesCalcifediolmedicine.symptomBiotechnologymedicine.drug

description

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.

10.1016/j.ejpb.2016.11.026https://hdl.handle.net/10033/621313