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Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads
C Faber1, H P Stallmann, D M Lyaruu
1Department of Orthopaedic Surgery, Vrije Universiteit Medical Center (VUMC), Vrije Universiteit, Amsterdam, The Netherlands. c.faber.icb.acta@med.vu.nl
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.
Insights
Antimicrobial peptides like Dhvar-5 show promise for treating osteomyelitis. Released from polymethylmethacrylate beads, Dhvar-5 maintains its effectiveness against resistant bacteria, offering a potential new local antibiotic therapy.
Area of Science:
- Orthopaedic Surgery
- Biomaterials Science
- Infectious Diseases
Background:
- Osteomyelitis presents significant morbidity and treatment challenges in orthopaedic surgery.
- Current treatments combining systemic and local antibiotics face antimicrobial resistance issues.
- Antimicrobial peptides (AMPs) offer a novel therapeutic avenue due to their low resistance potential.
Purpose of the Study:
- To evaluate the release kinetics of the antimicrobial peptide Dhvar-5 from polymethylmethacrylate (PMMA) beads.
- To assess the antimicrobial activity of released Dhvar-5 against methicillin-resistant Staphylococcus aureus (MRSA).
- To explore Dhvar-5/PMMA beads as a potential local treatment for osteomyelitis.
Main Methods:
- Incorporation of varying amounts of Dhvar-5 (120, 600, 1200 microg) into PMMA mini beads.
- Quantification of Dhvar-5 release from beads over 7 and 28 days.
- In vitro testing of released Dhvar-5's bactericidal activity against a clinical MRSA isolate.
Main Results:
- Dhvar-5 was successfully released from PMMA beads in all tested concentrations.
- Release amounts showed an exponential relationship with incorporated peptide, not linear.
- Released Dhvar-5 retained significant antimicrobial activity against MRSA.
Conclusions:
- PMMA beads can effectively deliver Dhvar-5 for localized antimicrobial action.
- The release profile of Dhvar-5 from PMMA beads is concentration-dependent and sustained.
- Dhvar-5 demonstrates potential as a novel, resistance-evading agent for osteomyelitis treatment.