Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms

Inês Santos Ferreira,1 Ana F Bettencourt,1 Lídia MD Gonçalves,1 Stefanie Kasper,2 Bertrand Bétrisey,3 Judith Kikhney,2 Annette Moter,2 Andrej Trampuz,4 António J Almeida1 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Univ...

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Autores principales:	Santos Ferreira I, Bettencourt AF, Gonçalves LMD, Kasper S, Bétrisey B, Kikhney J, Moter A, Trampuz A, Almeida AJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6bbc171a1de74289b9ed0d5052fe9da9
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spelling	oai:doaj.org-article:6bbc171a1de74289b9ed0d5052fe9da92021-12-02T00:45:55ZActivity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms1178-2013https://doaj.org/article/6bbc171a1de74289b9ed0d5052fe9da92015-07-01T00:00:00Zhttp://www.dovepress.com/activity-of-daptomycin--and-vancomycin-loaded-poly-epsilon-caprolacton-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Inês Santos Ferreira,1 Ana F Bettencourt,1 Lídia MD Gonçalves,1 Stefanie Kasper,2 Bertrand Bétrisey,3 Judith Kikhney,2 Annette Moter,2 Andrej Trampuz,4 António J Almeida1 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; 2Biofilmcenter, German Heart Institute Berlin, Berlin, Germany; 3Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 4Center for Musculoskeletal Surgery, Charité – University Medicine Berlin, Berlin, Germany Abstract: The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micrometer size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal microcalorimetry also revealed that lower concentrations of daptomycin-loaded microparticles were required to completely inhibit the recovery of mature MRSA and S. epidermidis biofilms. Further characterization of the effect of daptomycin-loaded PCL microparticles on mature biofilms was performed by fluorescence in situ hybridization. Fluorescence in situ hybridization showed an important reduction in MRSA biofilm, whereas S. epidermidis biofilms, although inhibited, were not eradicated. In addition, an important attachment of the microparticles to MRSA and S. epidermidis biofilms was observed. Finally, all formulations proved to be biocompatible with both ISO compliant L929 fibroblasts and human MG63 osteoblast-like cells.Keywords: antibiotic release, Staphylococcus aureus, Staphylococcus epidermidis, fluorescence in situ hybridization, isothermal microcalorimetrySantos Ferreira IBettencourt AFGonçalves LMDKasper SBétrisey BKikhney JMoter ATrampuz AAlmeida AJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4351-4366 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Santos Ferreira I Bettencourt AF Gonçalves LMD Kasper S Bétrisey B Kikhney J Moter A Trampuz A Almeida AJ Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
description	Inês Santos Ferreira,1 Ana F Bettencourt,1 Lídia MD Gonçalves,1 Stefanie Kasper,2 Bertrand Bétrisey,3 Judith Kikhney,2 Annette Moter,2 Andrej Trampuz,4 António J Almeida1 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; 2Biofilmcenter, German Heart Institute Berlin, Berlin, Germany; 3Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 4Center for Musculoskeletal Surgery, Charité – University Medicine Berlin, Berlin, Germany Abstract: The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micrometer size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal microcalorimetry also revealed that lower concentrations of daptomycin-loaded microparticles were required to completely inhibit the recovery of mature MRSA and S. epidermidis biofilms. Further characterization of the effect of daptomycin-loaded PCL microparticles on mature biofilms was performed by fluorescence in situ hybridization. Fluorescence in situ hybridization showed an important reduction in MRSA biofilm, whereas S. epidermidis biofilms, although inhibited, were not eradicated. In addition, an important attachment of the microparticles to MRSA and S. epidermidis biofilms was observed. Finally, all formulations proved to be biocompatible with both ISO compliant L929 fibroblasts and human MG63 osteoblast-like cells.Keywords: antibiotic release, Staphylococcus aureus, Staphylococcus epidermidis, fluorescence in situ hybridization, isothermal microcalorimetry
format	article
author	Santos Ferreira I Bettencourt AF Gonçalves LMD Kasper S Bétrisey B Kikhney J Moter A Trampuz A Almeida AJ
author_facet	Santos Ferreira I Bettencourt AF Gonçalves LMD Kasper S Bétrisey B Kikhney J Moter A Trampuz A Almeida AJ
author_sort	Santos Ferreira I
title	Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
title_short	Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
title_full	Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
title_fullStr	Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
title_full_unstemmed	Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
title_sort	activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/6bbc171a1de74289b9ed0d5052fe9da9
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Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms

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