title: Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads.
abstract: Osteomyelitis is still a major cause of morbidity and remains a difficult complication to treat in orthopaedic surgery. The treatment of choice is a combination of systemic and local antibiotics. The insertion of gentamicin-loaded polymethylmethacrylate (PMMA) beads into the bone results in high local concentrations of gentamicin and low systemic concentrations. However, the effectiveness of this treatment is being hampered by the emergence of antimicrobial resistance. New antimicrobial agents are therefore needed. One new class of promising antibiotics is antimicrobial peptides (AMP). Derived from natural human peptides, these have a low tendency to induce antimicrobial resistance. Dhvar-5 is an antimicrobial peptide based on histatin-5, which is found in human saliva and consists of 14 amino acids. It has demonstrated bactericidal activity in vitro. In order to develop a new local treatment using Dhvar-5 for osteomyelitis, we investigated its release from PMMA beads and its antimicrobial activity against a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA) before and after release from PMMA beads. Specific amounts of Dhvar-5 were incorporated into PMMA mini beads, containing 120, 600 and 1200 microg of Dhvar-5, respectively. Dhvar-5 was released from the beads in all three groups. Total release from the 120 microg beads was 9 microg per bead after 7 days. However, the release per bead in the 600 and 1200 microg beads was far more, respectively, 416 and 1091 microg over a 28 day period. After release, the Dhvar-5 also retained its antimicrobial activity against MRSA. On the basis of these data we conclude that the amount of Dhvar-5 release from PMMA beads is not proportionate to the amount incorporated; instead, it demonstrated an exponential relationship to the amount of total peptide released. Furthermore, the released peptide remained biologically active against a clinical isolate of MRSA.
authors.affiliation: Department of Orthopaedic Surgery, Vrije Universiteit Medical Center (VUMC), Vrije Universiteit, Amsterdam, The Netherlands. c.faber.icb.acta@med.vu.nl
authors.forename: C
authors.initials: C
authors.lastname: Faber
authors.forename: H P
authors.initials: HP
authors.lastname: Stallmann
authors.forename: D M
authors.initials: DM
authors.lastname: Lyaruu
authors.forename: J M A
authors.initials: JM
authors.lastname: de Blieck
authors.forename: Th J M
authors.initials: TJ
authors.lastname: Bervoets
authors.forename: A
authors.initials: A
authors.lastname: van Nieuw Amerongen
authors.forename: P I J M
authors.initials: PI
authors.lastname: Wuisman
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D054808:Histatins; D006801:Humans; D008863:Microspheres; D010019:Osteomyelitis / Q000188:drug therapy; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; C068075:HTN3 protein, human; D054808:Histatins; D010455:Peptides; D011109:Polymethacrylic Acids; D012471:Salivary Proteins and Peptides; C030613:polymethacrylic acid