title: In vitro elution of vancomycin from biodegradable osteoconductive calcium phosphate-polycaprolactone composite beads for treatment of osteomyelitis.
abstract: In this work, osteoconductive composite materials comprising a large volume fraction of a bioresorbable calcium phosphate ceramic (CaP) and a smaller amount of a polycaprolactone polymer (PCL) were studied as a degradable antibiotic carrier material for treatment of osteomyelitis. Beads loaded with 1 and 4wt.% vancomycin were prepared by admixing dissolved drug to an in situ synthesized dicalcium phosphate (DCP)-PCL or solution-mixed beta-tricalcium phosphate (βTCP)-PCL composite powder followed by high pressure consolidation of the blend at room temperature. Vancomycin release was measured in phosphate-buffered saline (PBS) at 37°C. All the beads gradually released the drug over the period of 4-11weeks, depending on the composite matrix homogeneity and porosity. Mathematical modeling using the Peppas equation showed that vancomycin elution was diffusion controlled. The stability of the antibiotic after high pressure application at room temperature was demonstrated by high-performance liquid chromatography-mass spectrometry (HPLC-MS) studies and MIC testing. The preservation of the structure and activity of vancomycin during the processing of composite beads and its sustained in vitro release profile suggest that high pressure consolidated CaP-PCL beads may be useful in the treatment of chronic bone infections as resorbable delivery vehicles of vancomycin and even of thermally unstable drug substances.
authors.affiliation: Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: C
authors.initials: C
authors.lastname: Makarov
authors.affiliation: Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: V
authors.initials: V
authors.lastname: Cohen
authors.affiliation: Rambam Health Care Campus and Faculty of Medicine, Technion, Haifa 31096, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Raz-Pasteur
authors.affiliation: Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: gotman@tx.technion.ac.il.
authors.forename: I
authors.initials: I
authors.lastname: Gotman
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry*; D010019:Osteomyelitis / Q000188:drug therapy; D011091:Polyesters / Q000737:chemistry*; D011312:Pressure; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D002130:Calcium Phosphates; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D014640:Vancomycin; C020243:calcium phosphate
keywords: Bioresorbable; Calcium phosphate; Composite material; Drug release; Osteomyelitis; Polycaprolactone