In vitro activity of Vancomycin-loaded nanodroplets against Enterococcus spp

Introduction: Chronic wounds (diabetic, venous and pressure ulcers) represent an increasingly growing emergency among the elderly in Western countries. Persistent hypoxia is one of the main clinical features of chronic wounds and infections can cause either a delay in wound healing or worsening of the wound. Adjunct therapies to facilitate chronic wounds to heal or to prevent their infections are urgently needed. In this context, oxygen-loaded nanodroplets (OLNDs) and vancomycin-loaded nanodroplets (VLNDs) have been proposed to counteract hypoxia effects and to deliver the antibiotic to bacteria, respectively. Nanodroplets (NDs) also display per se antimicrobial properties due to chitosan’s presence in the outer shell. Skin infections are caused by different microbial agents including Enterococcus spp. In the present work, the activities of VLNDs and OLNDs were evaluated against Eterococcus spp in normoxia and hypoxia. Materials and Methods: Eight strains of the E. faecalis and E. faecium isolated from infected wounds were cultivated in normoxic or hypoxic conditions. The antibacterial activity of free vancomycin, VLNDs or OLNDs was defined as the minimum inhibitory concentration (MIC), and determined through the microdilution broth method. The minimal bactericidal concentration (MBC) was also evaluated. Results: Six out of the eight isolated strains exhibited sensitivity to vancomycin (MICs 0.5-1μg/ml), whereas two of them were resistant (MIC>256µg/ml). A slight decrease of the growth of 4 strains was observed in hypoxic condition. When OLNDs were added to the broth, increased growth of bacteria in hypoxic condition was observed. The MIC and MBC values for vancomycin were comparable in normoxic and hypoxic conditions. VLNDs showed better activity than free vancomycin against the Enterococcus spp and, at the effective concentrations on bacteria, no toxicity on the human cells was seen. Conclusions: VLNDs were more effective than free vancomycin against E. faecalis and E. faecium and this may be due to the prolonged drug release profile. These data indicate that VLNDs can be promising tools for the topical treatment of infected and chronic ulcers.