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

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.
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. Basilico, R. Cavalli, and M. Prato.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1698478
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