Background: Streptococcus pyogenes infections vary from superficial infection of the pharynx to serious skin and soft tissue infections that can lead to lethal invasive disease, despite antibiotic treatment. The use of nanoparticles has advantages in treating many dermatological conditions. Nanoparticle applications facilitate the body’s response to foreign pathogens by improving innate and adaptive immune responses, increasing the effectiveness and reducing the adverse effects of antimicrobials and other therapeutic agents. Here, we evaluated erythromycin-loaded nanodroplet (Ery-LND) potential as adjuvant therapeutics for infected chronic wounds by investigating their antimicrobial activity against Streptococcus pyogenes, along with toxicity on human keratinocytes. Materials/methods: Low molecular weight chitosan-shelled and 2H,3H-decafluoropentane-cored nanodroplets (NDs), both oxygen-free (OFNDs) and oxygen-loaded (OLNDs), and Ery-LNDs were prepared and characterized for physico-chemical parameters and drug release kinetics. Subsequently all NDs were tested for biocompatibility with human skin cells and for their antibacterial properties or interactions with erythromycin susceptible S. pyogenes. Complementary analysis by confocal microscopy was also performed to study the physical interaction between NDs and cell wall/membranes. Bacterial growth was monitored upon incubation with/without NDs for increasing times (4, 6, 24 hours). Results: All NDs were not toxic to keratinocytes. Analysis by confocal microscopy showed OLND and OFND internalization by S. pyogenes already after 3 h of incubation (Figure 1). According to cell counts, OLNDs and OFNDs displayed long term antimicrobial efficacy against S. pyogenes significantly inhibiting bacterial growth up to 24 h, thank to known chitosan antimicrobial properties. Intriguingly, Ery-LNDs were generally more effective than erythromycin alone in counteract streptococcal growth, probably due to Ery-LNDs internalization by bacteria. Conclusions: Taken together, these results support the hypothesis that NDs are capable antibacterial/skin-friendly devices and proper Ery-NDs might be a promising strategy for the topical treatment of streptococcal skin infections.

Low molecular weight chitosan nanodroplets as promising strategy for controlled antibiotic delivery against Streptococcus pyogenes skin infections

G. Banche;V. Allizond;N. Finesso;M. Argenziano;A. Luganini;G. Giribaldi;A. Khadjavi;M. R. Iannantuoni;V. Tullio;N. Mandras;M. Prato;R. Cavalli;A. M. Cuffini
2018

Abstract

Background: Streptococcus pyogenes infections vary from superficial infection of the pharynx to serious skin and soft tissue infections that can lead to lethal invasive disease, despite antibiotic treatment. The use of nanoparticles has advantages in treating many dermatological conditions. Nanoparticle applications facilitate the body’s response to foreign pathogens by improving innate and adaptive immune responses, increasing the effectiveness and reducing the adverse effects of antimicrobials and other therapeutic agents. Here, we evaluated erythromycin-loaded nanodroplet (Ery-LND) potential as adjuvant therapeutics for infected chronic wounds by investigating their antimicrobial activity against Streptococcus pyogenes, along with toxicity on human keratinocytes. Materials/methods: Low molecular weight chitosan-shelled and 2H,3H-decafluoropentane-cored nanodroplets (NDs), both oxygen-free (OFNDs) and oxygen-loaded (OLNDs), and Ery-LNDs were prepared and characterized for physico-chemical parameters and drug release kinetics. Subsequently all NDs were tested for biocompatibility with human skin cells and for their antibacterial properties or interactions with erythromycin susceptible S. pyogenes. Complementary analysis by confocal microscopy was also performed to study the physical interaction between NDs and cell wall/membranes. Bacterial growth was monitored upon incubation with/without NDs for increasing times (4, 6, 24 hours). Results: All NDs were not toxic to keratinocytes. Analysis by confocal microscopy showed OLND and OFND internalization by S. pyogenes already after 3 h of incubation (Figure 1). According to cell counts, OLNDs and OFNDs displayed long term antimicrobial efficacy against S. pyogenes significantly inhibiting bacterial growth up to 24 h, thank to known chitosan antimicrobial properties. Intriguingly, Ery-LNDs were generally more effective than erythromycin alone in counteract streptococcal growth, probably due to Ery-LNDs internalization by bacteria. Conclusions: Taken together, these results support the hypothesis that NDs are capable antibacterial/skin-friendly devices and proper Ery-NDs might be a promising strategy for the topical treatment of streptococcal skin infections.
28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
Madrid
21-24 April 2018
ESCMID eLibrary
ESCMID
P1252
P1252
https://www.escmid.org/escmid_publications/escmid_elibrary/
G. Banche, V. Allizond, N. Finesso, M. Argenziano, A. Luganini, A. Troia, G. Giribaldi, A. Khadjavi, M.R. Iannantuoni, V. Tullio, N. Mandras, M. Prato, R. Cavalli, A.M. Cuffini
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1678122
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