Persistent hypoxia is a main clinical feature of chronic wounds. Intriguingly, oxygen-loaded nanodroplets (OLNDs) - filled with oxygen-binding 2H,3H-decafluoropentane and shelled with changeable polysaccharides - were proposed as promising tools to counteract hypoxia by releasing clinically relevant oxygen doses in a time-sustained manner. Here, different chitosan species/derivatives [medium or low weight (MW or LW), glycol- (G), and methylglycol- (MG) chitosan] were compared as candidate biomaterials for shell manufacturing to optimise OLND physico-chemical characteristics, biocompatibility, and efficacy. All OLND formulations displayed spherical morphology, cationic surfaces, ≤ 500 nm diameters (with LW chitosan-shelled OLNDs being the smallest), high stability (with G chitosan-shelled OLNDs being the less stable), good oxygen encapsulation efficiency, and prolonged oxygen release kinetics. MW, LW, and G chitosan were generally not toxic to human keratinocytes (HaCaT cell line), whereas MG chitosan reduced cell viability by 50%. Based on all these results, only LW and MW chitosan-shelled OLND formulations were comparatively analysed in the subsequent biological experiments. Both LW and MW chitosan-shelled OLNDs effectively improved migration of hypoxic keratinocytes. However, LW chitosan-shelled OLNDs appeared significantly less toxic to HaCaT cells than MW chitosan-shelled OLNDs. Therefore, LW chitosan emerges as the best candidate biomaterial to be employed for future OLND manufacturing.

New perspectives to counteract hypoxia in chronic wounds: a comparative evaluation of physico-chemistry, biocompatibility, and efficacy of oxygen-loaded nanodroplets shelled with different chitosan species and derivatives.

M. Argenziano;N. Finesso;T. Genova;G. Giribaldi;C. Guiot;A. M. Cuffini;R. Cavalli;
2018-01-01

Abstract

Persistent hypoxia is a main clinical feature of chronic wounds. Intriguingly, oxygen-loaded nanodroplets (OLNDs) - filled with oxygen-binding 2H,3H-decafluoropentane and shelled with changeable polysaccharides - were proposed as promising tools to counteract hypoxia by releasing clinically relevant oxygen doses in a time-sustained manner. Here, different chitosan species/derivatives [medium or low weight (MW or LW), glycol- (G), and methylglycol- (MG) chitosan] were compared as candidate biomaterials for shell manufacturing to optimise OLND physico-chemical characteristics, biocompatibility, and efficacy. All OLND formulations displayed spherical morphology, cationic surfaces, ≤ 500 nm diameters (with LW chitosan-shelled OLNDs being the smallest), high stability (with G chitosan-shelled OLNDs being the less stable), good oxygen encapsulation efficiency, and prolonged oxygen release kinetics. MW, LW, and G chitosan were generally not toxic to human keratinocytes (HaCaT cell line), whereas MG chitosan reduced cell viability by 50%. Based on all these results, only LW and MW chitosan-shelled OLND formulations were comparatively analysed in the subsequent biological experiments. Both LW and MW chitosan-shelled OLNDs effectively improved migration of hypoxic keratinocytes. However, LW chitosan-shelled OLNDs appeared significantly less toxic to HaCaT cells than MW chitosan-shelled OLNDs. Therefore, LW chitosan emerges as the best candidate biomaterial to be employed for future OLND manufacturing.
2018
Keystone Symposium “Therapeutic Targeting of Hypoxia-Sensitive Pathways”
University of Oxford Mathematical Institute, Oxford, UK
10-14/04/2018
Abstract book
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P2025
83
83
M. Argenziano, N. Finesso, S. D’Alessandro, M. Fumagalli, E. Sangiovanni, T. Genova, A. Troia, G. Giribaldi, C. Guiot, A.M. Cuffini, M. Dell’Agli, N. ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1698478
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