title: Development of advanced biantibiotic loaded bone cement spacers for arthroplasty associated infections.
abstract: The incidence increase of infections in patients with hip or knee implants with resistant pathogens (mainly some S. coagulase-negative and gram positive bacteria) demands advanced antibiotic loaded formulations. In this paper, we report the design of new biantibiotic acrylic bone cements for in situ delivery. They include a last generation antibiotic (daptomycin or linezolid) in combination with vancomycin and are performed based on a novel modification of the Palacos R®acrylic bone cement, which is based on two components, a liquid (methyl methacrylate) and a solid (polymeric phase). Hence, the solid component of the experimental formulations include 45wt% of microparticles of poly(D,L-lactic-co-glycolic) acid, 55wt% of poly(methyl methacrylate) beads and supplements (10wt-% each) of antibiotics. These formulations provide a selective and excellent control of the local release of antibiotics during a long time period (up to 2 months), avoiding systemic dissemination. The antimicrobial activity of the advanced spacers tested against S. aureus shows that single doses would be enough for the control of the infection. In vitro biocompatibility of cements on human osteoblasts is ensured. This paper is mainly focused on the preparation and characterization of cements and the studies of elution kinetics and bactericidal effects. Developed formulations are proposed as spacers for the treatment of infected arthroplasties, but also, they could be applied in other antibiotic devices to treat relevant bone-related infection diseases.
authors.affiliation: Institute of Polymer Science and Technology, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain; CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Parra-Ruíz
authors.affiliation: Institute of Polymer Science and Technology, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain; CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: González-Gómez
authors.affiliation: Institute of Polymer Science and Technology, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain; CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Gutiérrez
authors.affiliation: Institute of Polymer Science and Technology, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain; CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain; Clinical Research and Experimental Biopathology Unit, (CHA.SACyL), "Associate Unit to CSIC", Av. Juan Carlos I s/n, 05071 Ávila, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Parra
authors.affiliation: Hospital Príncipe de Asturias of Alcalá de Henares, Ctra de Alcalá-Meco s/n 28805, Alcalá de Henares, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: García-García
authors.affiliation: Hospital of Guadalajara University, C/Donante de Sangre, s/n, 19002 Guadalajara, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Azuara
authors.affiliation: Ramón y Cajal Hospital, Ctra. de Colmenar Viejo, km. 9, 100, 28034 Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: De la Torre
authors.affiliation: CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain; Faculty of Medicine, Alcalá de Henares University, University Campus - C/19, Ctra. Madrid-Barcelona, Km 33,600, 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Buján
authors.affiliation: Faculty of Medicine, Alcalá de Henares University, University Campus - C/19, Ctra. Madrid-Barcelona, Km 33,600, 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Ibarra
authors.affiliation: LVD BIOTECH S.L., Camí de Can Ubach 11, Pol. Ind. Les Fallulles, Sant Vicenç Dels Horts, 08620 Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Duocastella-Codina
authors.affiliation: LVD BIOTECH S.L., Camí de Can Ubach 11, Pol. Ind. Les Fallulles, Sant Vicenç Dels Horts, 08620 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Molina-Crisol
authors.affiliation: Institute of Polymer Science and Technology, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain; CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain. Electronic address: bvazquez@ictp.csic.es.
authors.forename: B
authors.initials: B
authors.lastname: Vázquez-Lasa
authors.affiliation: Institute of Polymer Science and Technology, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain; CIBER, Health Institute Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: San Román
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001178:Arthroplasty / Q000009:adverse effects*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D001843:Bone Cements; D017576:Daptomycin / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D004339:Drug Compounding; D006801:Humans; D000069349:Linezolid / Q000008:administration & dosage / Q000494:pharmacology; D008422:Materials Testing; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D004338:Drug Combinations; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin
keywords: Acrylic bone cement spacers; Daptomycin; Infection; Linezolid; S. aureus.