ERS Respiratory Channel

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Abstract

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.

Abstract

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