Background: Chronic wounds (CWs) are typically characterized by persistent tissue hypoxia, exacerbated inflammation, and impaired matrix remodeling. Moreover, CWs are often worsened by microbial infections, with antimicrobial therapies being hindered by emerging resistant strains. The known benefits of nanotechnology combined with the advantages of antimicrobial properties of natural polysaccharides such as chitosan have paved the way for the development of new oxygen-based therapies to treat infected CWs. The specific aim of this work was to assess the antimicrobial effects of chitosan-based nanocarriers against bacteria. Materials/methods: Shell/core-structured oxygen nanocarriers [perfluoropentane (PFP)-cored nanobubbles and 2H,3H-decafluoropentane (DFP)-cored nanodroplets] were alternatively shelled with two chitosan molecules of different molecular weight [medium weight (MW) or low weight (LW) chitosan]. After manufacturing, MW chitosan-shelled oxygen-loaded nanobubbles (cOLNBs), as well as MW or LW chitosan-shelled oxygen-loaded nanodroplets (cOLNDs) were comparatively characterized for morphology and physico-chemical properties by microscopy and dynamic light scattering, respectively. In vitro oxygen releases from cOLNBs and cOLNDs or from control oxygen saturated-solution were comparatively measured through an oxymeter. Their biocompatibility and their ability to promote wound healing in human hypoxic skin cells were challenged by using keratinocyte, fibroblast, and/or endothelial cell lines. Their antimicrobial activity was investigated towards methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes clinical strains and measured by monitoring bacterial growth over time. For each microorganism, the mechanical interaction with nanocarriers was also assessed by confocal microscopy. Results: All carriers displayed spherical morphology, cationic surfaces, and diameters in the nanometer range. However, in vitro oxygen release from OLNDs appeared higher and more sustained over time than from OLNBs. Additionally, LW cOLNDs displayed lower toxicity to skin cells than MW chitosan-shelled carriers. Compared to MW cOLNBs/cOLNDs, LW cOLNDs displayed in general similar or better efficacy in promoting wound healing under hypoxic conditions and in inhibiting both staphylococcal and streptococcal growth, in a long-term manner as a consequence of early cellular internalization (Figure 1). Conclusions: Based on these findings, LW cOLNDs appear to be the most promising nanocarriers among those tested here to be potentially employed as innovative, nonconventional, and cost-effective medical devices for the treatment of hypoxic and infected CWs.

Antimicrobial and oxygenating nonconventional nanotherapies for the management of chronic wound infections

BANCHE Giuliana;ALLIZOND Valeria;MANDRAS Narcisa;FINESSO Nicole;ARGENZIANO Monica;LUGANINI Anna;GIRIBALDI Giuliana;KHADJAVI Amina;PRATO Mauro;TULLIO Vivian;CAVALLI Roberta;CUFFINI Anna Maria
2019

Abstract

Background: Chronic wounds (CWs) are typically characterized by persistent tissue hypoxia, exacerbated inflammation, and impaired matrix remodeling. Moreover, CWs are often worsened by microbial infections, with antimicrobial therapies being hindered by emerging resistant strains. The known benefits of nanotechnology combined with the advantages of antimicrobial properties of natural polysaccharides such as chitosan have paved the way for the development of new oxygen-based therapies to treat infected CWs. The specific aim of this work was to assess the antimicrobial effects of chitosan-based nanocarriers against bacteria. Materials/methods: Shell/core-structured oxygen nanocarriers [perfluoropentane (PFP)-cored nanobubbles and 2H,3H-decafluoropentane (DFP)-cored nanodroplets] were alternatively shelled with two chitosan molecules of different molecular weight [medium weight (MW) or low weight (LW) chitosan]. After manufacturing, MW chitosan-shelled oxygen-loaded nanobubbles (cOLNBs), as well as MW or LW chitosan-shelled oxygen-loaded nanodroplets (cOLNDs) were comparatively characterized for morphology and physico-chemical properties by microscopy and dynamic light scattering, respectively. In vitro oxygen releases from cOLNBs and cOLNDs or from control oxygen saturated-solution were comparatively measured through an oxymeter. Their biocompatibility and their ability to promote wound healing in human hypoxic skin cells were challenged by using keratinocyte, fibroblast, and/or endothelial cell lines. Their antimicrobial activity was investigated towards methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes clinical strains and measured by monitoring bacterial growth over time. For each microorganism, the mechanical interaction with nanocarriers was also assessed by confocal microscopy. Results: All carriers displayed spherical morphology, cationic surfaces, and diameters in the nanometer range. However, in vitro oxygen release from OLNDs appeared higher and more sustained over time than from OLNBs. Additionally, LW cOLNDs displayed lower toxicity to skin cells than MW chitosan-shelled carriers. Compared to MW cOLNBs/cOLNDs, LW cOLNDs displayed in general similar or better efficacy in promoting wound healing under hypoxic conditions and in inhibiting both staphylococcal and streptococcal growth, in a long-term manner as a consequence of early cellular internalization (Figure 1). Conclusions: Based on these findings, LW cOLNDs appear to be the most promising nanocarriers among those tested here to be potentially employed as innovative, nonconventional, and cost-effective medical devices for the treatment of hypoxic and infected CWs.
29th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
Amsterdam
13-16 April 2019
ESCMID eLibrary
ESCMID
O0434
O0434
https://www.escmid.org/escmid_publications/escmid_elibrary/
BANCHE Giuliana, ALLIZOND Valeria, MANDRAS Narcisa, FINESSO Nicole, ARGENZIANO Monica, LUGANINI Anna, TROIA Andriano, GIRIBALDI Giuliana, KHADJAVI Amina, PRATO Mauro, TULLIO Vivian, CAVALLI Roberta, CUFFINI Anna Maria
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1702524
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