title: A novel modified acrylic bone cement matrix. A step forward on antibiotic delivery against multiresistant bacteria responsible for prosthetic joint infections.
abstract: Currently the safe and responsible use of antibiotics is a world-wide concern as it promotes prevention of the increasing emergence of multiresistant bacterial strains. Considering that there is a noticeable decline of the available antibiotic pipeline able to combat emerging resistance in serious infection a major concern grows around the prosthetic joint infections once the available commercial antibiotic loaded polymethylmethacrylate bone cements (BC) are inadequate for local antibiotic treatment, especially against MRSA, the most commonly isolated and antibiotic-resistant pathogen in bone infections. In this paper a novel modified BC matrix loaded with minocycline is proposed. A renewed interest in this tetracycline arises due to its broad-spectrum of activity against the main organisms responsible for prosthetic joint infections, especially against MRSA. The modified BC matrices were evaluated concerning minocycline release profile, biomechanical properties, solid-state characterization, antimicrobial stability and biocompatibility under in vitro conditions. BC matrix loaded with 2.5% (w/wBC) of minocycline and 10.0% (w/wBC) of lactose presented the best properties since it completely released the loaded minocycline, maintained the mechanical properties and the antimicrobial activity against representative strains of orthopedic infections. In vitro biocompatibility was assessed for the elected matrix and neither minocycline nor lactose loading enhanced BC cytotoxicity.
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; School of Science and Health Technologies, University Lusófona, Campo Grande 376, 1749-024 Lisbon, Portugal. Electronic address: anamatos@ff.ul.pt.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Matos
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Lídia M
authors.initials: LM
authors.lastname: Gonçalves
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; School of Science and Health Technologies, University Lusófona, Campo Grande 376, 1749-024 Lisbon, Portugal; CBIOS, University Lusófona Research Center in Biosciences and Health Technologies, Campo Grande 376, 1749-024 Lisbon, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Rijo
authors.affiliation: INEGI, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n 4200-465 Porto, Portugal.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Vaz
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: António J
authors.initials: AJ
authors.lastname: Almeida
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Bettencourt
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006801:Humans; D007592:Joint Diseases / Q000188:drug therapy* / Q000382:microbiology; D008422:Materials Testing; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D019904:Polymethyl Methacrylate; D008911:Minocycline
keywords: Antibiotic release; Arthroplasty; Biocompatibility; Bone cement; Mechanical properties; Minocycline