Background. In the airways, the CFTR genetic defect leads to dysregulation of inflammatory and iron homeostasis that precedes bacterial infection that, in turn, worsens host damage. Lactoferrin (Lf), an iron-chelating glycoprotein of the innate immunity present in airway secretions and secreted by neutrophils in infection/inflammation sites, in addition to the well-known antibacterial activity exerts a key role in inflammatory and iron homeostasis.
Hypothesis and objectives. We suppose that aerosolized bLf can exert a key role on inflammatory and iron dysregulation and reduce infection in pre-clinical CF mouse models of lung infection. Moreover, since Lf is a natural molecule, it shows no side effects and toxicity. In this study we employed bovine milk derived Lf (bLf) as it has been yet used in several clinical trials. Since in CF airways human and bacterial proteases may alter Lf integrity reducing its activity, we hypothesize that nano-delivery of bLf can protect the molecule against proteolysis. The objectives are: 1- to evaluate anti-inflammatory and antibacterial activities of bLf administered by aerosol in mouse models of chronic lung infection; 2- to prepare bLf-loaded nanoparticles (bLf-NANOs) to be aerosolized.