PMID- 29488195 OWN - NLM STAT- MEDLINE DCOM- 20180829 LR - 20181202 IS - 1530-9932 (Electronic) IS - 1530-9932 (Linking) VI - 19 IP - 4 DP - 2018 May TI - Encapsulation in Polymeric Microparticles Improves Daptomycin Activity Against Mature Staphylococci Biofilms-a Thermal and Imaging Study. PG - 1625-1636 LID - 10.1208/s12249-018-0974-7 [doi] AB - Eradication of Gram-positive biofilms is a critical aspect in implant-associated infection treatment. Although antibiotic-containing particulate carriers may be a promising strategy for overcoming biofilm tolerance, the assessment of their interaction with biofilms has not been fully explored. In the present work, the antibiofilm activity of daptomycin- and vancomycin-loaded poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (EUD) microparticles against methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive S. epidermidis biofilms was investigated using isothermal microcalorimetry (IMC) and fluorescence in situ hybridization (FISH). The minimal biofilm inhibitory concentrations (MBIC) of MRSA biofilms, as determined by IMC, were 5 and 20 mg/mL for daptomycin- and vancomycin-loaded PMMA microparticles, respectively. S. epidermidis biofilms were less susceptible, with a MBIC of 20 mg/mL for daptomycin-loaded PMMA microparticles. Vancomycin-loaded microparticles were ineffective. Adding EUD to the formulation caused a 4- and 16-fold reduction of the MBIC values of daptomycin-loaded microparticles for S. aureus and S. epidermidis, respectively. FISH corroborated the IMC results and provided additional insights on the antibiofilm effect of these particles. According to microscopic analysis, only daptomycin-loaded PMMA-EUD microparticles were causing a pronounced reduction in biofilm mass for both strains. Taken together, although IMC indicated that a biofilm inhibition was achieved, microscopy showed that the biofilm was not eradicated and still contained FISH-positive, presumably viable bacteria, thus indicating that combining the two techniques is essential to fully assess the effect of microparticles on staphylococcal biofilms. FAU - Santos Ferreira, Ines AU - Santos Ferreira I AD - Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmacia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. FAU - Kikhney, Judith AU - Kikhney J AD - Biofilmcenter, Deutsches Herzzentrum Berlin, Charite-Universitatsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. AD - Institute for Microbiology and Hygiene, Charite-Universitatsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. FAU - Kursawe, Laura AU - Kursawe L AD - Biofilmcenter, Deutsches Herzzentrum Berlin, Charite-Universitatsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. FAU - Kasper, Stefanie AU - Kasper S AD - Biofilmcenter, Deutsches Herzzentrum Berlin, Charite-Universitatsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. FAU - Goncalves, Lidia M D AU - Goncalves LMD AD - Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmacia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. FAU - Trampuz, Andrej AU - Trampuz A AD - Center for Musculoskeletal Surgery, Charite-Universitatsmedizin Berlin, Free and Humboldt-University of Berlin, Chariteplatz 1, 10117, Berlin, Germany. FAU - Moter, Annette AU - Moter A AD - Biofilmcenter, Deutsches Herzzentrum Berlin, Charite-Universitatsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. FAU - Bettencourt, Ana Francisca AU - Bettencourt AF AD - Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmacia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. asimao@ff.ulisboa.pt. FAU - Almeida, Antonio J AU - Almeida AJ AD - Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmacia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. aalmeida@ff.ulisboa.pt. LA - eng PT - Journal Article DEP - 20180227 PL - United States TA - AAPS PharmSciTech JT - AAPS PharmSciTech JID - 100960111 RN - 0 (Anti-Bacterial Agents) RN - NWQ5N31VKK (Daptomycin) SB - IM MH - Anti-Bacterial Agents/administration & dosage/chemistry/metabolism MH - Biofilms/*drug effects/growth & development MH - Daptomycin/administration & dosage/*chemistry/metabolism MH - In Situ Hybridization, Fluorescence MH - Methicillin-Resistant Staphylococcus aureus/*drug effects/physiology MH - Microbial Sensitivity Tests/methods MH - *Microspheres MH - Staphylococcus epidermidis/*drug effects/physiology OTO - NOTNLM OT - daptomycin OT - fluorescence in situ hybridization OT - isothermal microcalorimetry OT - microencapsulation OT - staphylococcal biofilms EDAT- 2018/03/01 06:00 MHDA- 2018/08/30 06:00 CRDT- 2018/03/01 06:00 PHST- 2017/11/08 00:00 [received] PHST- 2018/02/11 00:00 [accepted] PHST- 2018/03/01 06:00 [pubmed] PHST- 2018/08/30 06:00 [medline] PHST- 2018/03/01 06:00 [entrez] AID - 10.1208/s12249-018-0974-7 [pii] AID - 10.1208/s12249-018-0974-7 [doi] PST - ppublish SO - AAPS PharmSciTech. 2018 May;19(4):1625-1636. doi: 10.1208/s12249-018-0974-7. Epub 2018 Feb 27.