title: Novel doped calcium phosphate-PMMA bone cement composites as levofloxacin delivery systems.
abstract: Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials to control the occurrence of bone and joint infections. However, the inexistence of alternative antibiotics other than those already commercially available and the poor ability to bind to bone tissue hampering its biological function are still major drawbacks of ALABCs clinical application. The concept of this research work is to develop a novel bone cement (BC) drug delivery system composed by Mg- and Sr-doped calcium phosphate (CaP) particles as drug carriers loaded into a lactose-modified acrylic BC, which, to the best of our knowledge, has never been reported. CaP particles are known to promote bone ingrowth and current research is focused on using these carriers as antibiotic delivery systems for the treatment of bone infections, like osteomyelitis. Levofloxacin is a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues and increasingly being recommended to manage bone-related infections. Also, the lactose-modified BC matrix, with a more porous structure, has already proved to enhance antibiotic release from the BC inner matrix. This novel BC composite biomaterial has shown improved mechanical integrity, biocompatibility maintenance, and sustained release of levofloxacin, with concentrations over the minimum inhibitory concentration values after a 48h while maintaining antibacterial activity over an 8-week period against Staphyloccocus aureus and Staphyloccocus epidermidis, common pathogens associated with bone infections.
authors.affiliation: iMed.ULisboa, Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Matos
authors.affiliation: Department of Materials and Ceramics Engineering, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Catarina F
authors.initials: CF
authors.lastname: Marques
authors.affiliation: iMed.ULisboa, Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Rosana V
authors.initials: RV
authors.lastname: Pinto
authors.affiliation: iMed.ULisboa, Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Isabel A C
authors.initials: IA
authors.lastname: Ribeiro
authors.affiliation: iMed.ULisboa, Research Institute for Medicines and Pharmaceutical Sciences, 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: 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: Department of Materials and Ceramics Engineering, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: J M F
authors.initials: JM
authors.lastname: Ferreira
authors.affiliation: iMed.ULisboa, Research Institute for Medicines and Pharmaceutical Sciences, 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 and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: asimao@ff.ulisboa.pt.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Bettencourt
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry*; D001843:Bone Cements / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D064704:Levofloxacin / Q000737:chemistry* / Q000494:pharmacology; D008422:Materials Testing / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D016062:Porosity; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D001843:Bone Cements; D002130:Calcium Phosphates; D004337:Drug Carriers; D064704:Levofloxacin; D019904:Polymethyl Methacrylate; C020243:calcium phosphate
keywords: Biocompatibility; Biphasic calcium phosphate; Controlled release; Drug delivery system; Fluoroquinolone; Osteomyelitis; Poly(methylmethacrylate)