Bronchiolitis obliterans syndrome (BOS), caused by lung allograft-derived mesenchymal cells’ abnormal proliferation and extracellular matrix deposition, is the main cause of lung allograft rejection. In this study, a mild one-step ionotropic gelation method was set up to nanoencapsulate the everolimus, a key molecule in allograft organ rejection prevention, into hyaluronic acid-decorated chitosan-based nanoparticles. Rationale was the selective delivery of everolimus into lung allograft-derived mesenchymal cells; these cells are characterized by the CD44-overexpressing feature, and hyaluronic acid has proven to be a natural selective CD44-targeting moiety. The optimal process conditions were established by a design of experiment approach (full factorial design) aiming at the control of the nanoparticle size (200 nm), minimizing the size polydispersity (PDI 0.171 0.04), and at the negative potential maximization (30.9 mV). The everolimus was successfully loaded into hyaluronic acid-decorated chitosan-based nanoparticles (95.94 13.68 g/100 mg nanoparticles) and in vitro released in 24 h. The hyaluronic acid decoration on the nanoparticles provided targetability to CD44-overexpressing mesenchymal cells isolated from bronchoalveolar lavage of BOS-affected patients. The mesenchymal cells’ growth tests along with the nanoparticles uptake studies, at 37°C and 4°C, respectively, demonstrated a clear improvement of everolimus inhibitory activity when it is encapsulated in hyaluronic acid-decorated chitosan-based nanoparticles, ascribable to their active uptake mechanism.

Hyaluronic acid-decorated chitosan nanoparticles for CD44-targeted delivery of everolimus

Chiesa, Enrica;Dorati, Rossella;Conti, Bice;Modena, Tiziana;Cova, Emanuela;Meloni, Federica;Genta, Ida
2018-01-01

Abstract

Bronchiolitis obliterans syndrome (BOS), caused by lung allograft-derived mesenchymal cells’ abnormal proliferation and extracellular matrix deposition, is the main cause of lung allograft rejection. In this study, a mild one-step ionotropic gelation method was set up to nanoencapsulate the everolimus, a key molecule in allograft organ rejection prevention, into hyaluronic acid-decorated chitosan-based nanoparticles. Rationale was the selective delivery of everolimus into lung allograft-derived mesenchymal cells; these cells are characterized by the CD44-overexpressing feature, and hyaluronic acid has proven to be a natural selective CD44-targeting moiety. The optimal process conditions were established by a design of experiment approach (full factorial design) aiming at the control of the nanoparticle size (200 nm), minimizing the size polydispersity (PDI 0.171 0.04), and at the negative potential maximization (30.9 mV). The everolimus was successfully loaded into hyaluronic acid-decorated chitosan-based nanoparticles (95.94 13.68 g/100 mg nanoparticles) and in vitro released in 24 h. The hyaluronic acid decoration on the nanoparticles provided targetability to CD44-overexpressing mesenchymal cells isolated from bronchoalveolar lavage of BOS-affected patients. The mesenchymal cells’ growth tests along with the nanoparticles uptake studies, at 37°C and 4°C, respectively, demonstrated a clear improvement of everolimus inhibitory activity when it is encapsulated in hyaluronic acid-decorated chitosan-based nanoparticles, ascribable to their active uptake mechanism.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1224069
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