JAC Advance Access originally published online on April 25, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 1359-1364
© 2003 The British Society for Antimicrobial Chemotherapy
Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads
1 Department of Orthopaedic Surgery, Vrije Universiteit Medical Center (VUMC), Amsterdam; Departments of 2 Oral Cell Biology and 3 Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit, Amsterdam, The Netherlands
Received 5 November 2002; returned 6 December 2002; revised 16 January 2003; accepted 18 March 2003
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 µg of Dhvar-5, respectively. Dhvar-5 was released from the beads in all three groups. Total release from the 120 µg beads was 9 µg per bead after 7 days. However, the release per bead in the 600 and 1200 µg beads was far more, respectively, 416 and 1091 µg 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.
Keywords: antimicrobial peptides, Dhvar-5, PMMA beads, release kinetics
* Corresponding author. Tel: +31-20-4448662; Fax: +31-20-4448683; E-mail: c.faber.ocb.acta{at}med.vu.nl
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