Hyaluronic acid decorated-liposome loaded with Imatinib: an in vitro study as targeted drug delivery system for lung fibrosis

Background: Nanotechnology allows to deliver high concentrated drugs locally and to target specific cells promising a new therapeutic approach for interstitial lung fibrosis. We patented hyaluronic acid coated imatinib loaded liposomes (XHALIP) which aim to target CD44+ cells for inhalatory treatment of fibrogenic lung disorders. Aim: Assess XHALIP uptake and biological activity on respiratory effectors related to CD44 expression, comparing XHALIP to HA-uncoated liposomes (LIP). Methods: We analyzed liposomal biological activity (cell viability by MTT test and c-Abl inhibition) and their uptake (flow cytometry and confocal microscopy) in lung cells (macrophages, Lung Fibroblast derived from BAL (LF), A549 and 16HBE cells). Results: XHALIP uptake from different respiratory cells (Fig.1) was significantly higher (100X with respect to LIP) with XHALIP. 24 hours after treatment most of the internalized XHALIP co-localized with cellular endosomes. XHALIP also reduced LF viability by 30% up to 72 hrs while imatinib free drug was more toxic (up to 80% at 72hrs). On the other hand, XHALIP were able to impair Collagen1a1 release (65%) and c-abl phosphorylation up to 60% after a shot of 24 hrs treatment. Conclusion: XHALIP target and deliver drugs to lung pathogenic cells in vitro and represent a promising therapeutic option for the local treatment of fibrogenic lung disorders to be further developed.