PMID- 30153487
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 550
IP  - 1-2
DP  - 2018 Oct 25
TI  - Acrylic microparticles increase daptomycin intracellular and in vivo anti-biofilm 
      activity against Staphylococcus aureus.
PG  - 372-379
LID - S0378-5173(18)30626-4 [pii]
LID - 10.1016/j.ijpharm.2018.08.048 [doi]
AB  - Daptomycin (DAP) is a cyclic lipopeptide antibiotic with potential clinical 
      application in orthopedic infections caused by staphylococci. However, it failed 
      to eradicate Staphylococcus aureus in vitro, in intracellular infection studies, 
      as well as in vivo in an experimental model of implant-associated biofilm 
      infections. In this study, the antimicrobial effect of DAP encapsulated in 
      poly(methyl methacrylate)-Eudragit (PMMA-EUD) microparticles (DAP-MPs) on 
      intracellular S. aureus was evaluated in human osteoblast cells using 
      fluorescence in situ hybridization (FISH) analysis. Encapsulated DAP was able to 
      reduce the amount of intracellular S. aureus by 73% compared to blank 
      microparticles (MPs). Then, the advantage of treating with DAP-MPs versus free 
      DAP was evaluated in a murine model of implant-associated biofilm infection. Free 
      DAP showed a >3 log(10) decrease in planktonic and adherent bacteria but failed 
      to eradicate adherent methicillin-resistant S. aureus (MRSA), whereas DAP-MPs 
      showed a clearance of planktonic MRSA, significantly reduced adherent MRSA by 
      more than 3 log(10) and cured the infection in 60%. This was linked to the 
      prolonged higher DAP concentration within the tissue cage fluid compared to free 
      DAP. To our knowledge, this study provides the first evidence for the high 
      intracellular and in vivo anti-biofilm efficacy of DAP-MPs to target 
      staphylococcal infections.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Woischnig, Anne-Kathrin
AU  - Woischnig AK
AD  - Laboratory of Infection Biology, Department of Biomedicine, University and 
      University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
FAU - Goncalves, Lidia M
AU  - Goncalves LM
AD  - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
      Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal; 
      Cardiovascular Centre of the University of Lisbon, Faculty of Medicine, 
      Universidade de Lisboa, Av Prof. Egas Moniz, 1649-028 Lisbon, Portugal.
FAU - Ferreira, Maxime
AU  - Ferreira M
AD  - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
      Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
FAU - Kuehl, Richard
AU  - Kuehl R
AD  - Laboratory of Infection Biology, Department of Biomedicine, University and 
      University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Division of 
      Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, 
      Petersgraben 4, 4031 Basel, Switzerland.
FAU - Kikhney, Judith
AU  - Kikhney J
AD  - Biofilmcenter, Deutsches Herzzentrum Berlin, Charite - Universitatsmedizin 
      Berlin, Hindenburgdamm 30, 12203 Berlin, Germany; Institute for Microbiology, 
      Charite - Universitatsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
FAU - Moter, Annette
AU  - Moter A
AD  - Biofilmcenter, Deutsches Herzzentrum Berlin, Charite - Universitatsmedizin 
      Berlin, Hindenburgdamm 30, 12203 Berlin, Germany; Institute for Microbiology, 
      Charite - Universitatsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
FAU - Ribeiro, Isabel A C
AU  - Ribeiro IAC
AD  - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
      Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
FAU - Almeida, Antonio J
AU  - Almeida AJ
AD  - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
      Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
FAU - Khanna, Nina
AU  - Khanna N
AD  - Laboratory of Infection Biology, Department of Biomedicine, University and 
      University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Division of 
      Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, 
      Petersgraben 4, 4031 Basel, Switzerland.
FAU - Bettencourt, Ana Francisca
AU  - Bettencourt AF
AD  - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
      Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. 
      Electronic address: asimao@ff.ulisboa.pt.
LA  - eng
PT  - Journal Article
DEP - 20180825
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Acrylic Resins)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Polymers)
RN  - 33434-24-1 (Eudragit RS)
RN  - NWQ5N31VKK (Daptomycin)
SB  - IM
MH  - Acrylic Resins/administration & dosage
MH  - Animals
MH  - Anti-Bacterial Agents/*administration & dosage
MH  - Biofilms/drug effects
MH  - Cell Line
MH  - Daptomycin/*administration & dosage
MH  - Drug Carriers/*administration & dosage
MH  - Female
MH  - Humans
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects/physiology
MH  - Mice, Inbred C57BL
MH  - Osteoblasts/microbiology
MH  - Polymers/administration & dosage
MH  - Staphylococcal Infections/*drug therapy
OTO - NOTNLM
OT  - Microparticles
OT  - Mouse implant-associated biofilm infection model
OT  - Orthopedic associated-infection
OT  - Osteoblast
OT  - PMMA-Eudragit
EDAT- 2018/08/29 06:00
MHDA- 2019/01/08 06:00
CRDT- 2018/08/29 06:00
PHST- 2018/05/23 00:00 [received]
PHST- 2018/07/30 00:00 [revised]
PHST- 2018/08/24 00:00 [accepted]
PHST- 2018/08/29 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2018/08/29 06:00 [entrez]
AID - S0378-5173(18)30626-4 [pii]
AID - 10.1016/j.ijpharm.2018.08.048 [doi]
PST - ppublish
SO  - Int J Pharm. 2018 Oct 25;550(1-2):372-379. doi: 10.1016/j.ijpharm.2018.08.048. 
      Epub 2018 Aug 25.