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.

Adsorption behavior of antimicrobial peptide histatin 5 on PMMA

“…The limitations of this study are that the temperature was not physiological and the stability of adsorbed histatin 5 was not evaluated under oral environment. However, this study mainly focused on the adsorption behavior of histatin 5 onto PMMA using plasma treatment under controlled conditions 40 .…”

Preventive prospective of triclosan and triclosan-liposomal nanoparticles against experimental infection with a cystogenic ME49 strain of Toxoplasma gondii

“…According to Bangham (1980), Kirby and Gregoriadis (1984) and Faber et al (2003), TS liposomes solutions were prepared by the thin film hydration method, then were lyophilized and dried frozen. The distribution of particle size of TS-liposomes was determined by laser light scattering on a Beckman coulter particle size analyzer.…”

Salivary Proteins: Protective and Diagnostic Value in Cariology?

“…Years before the discovery of the magainins, it was reported that histidine-rich proteins in human saliva had killing activity against Candida albicans and S. mutans Pollock et al, 1984]. Since then most of the research on histatins has focussed on their fungicidal activity [Helmerhorst et al, 1997[Helmerhorst et al, , 1999Edgerton et al, 2000;Gyurko et al, 2001;Ruissen et al, 2001Ruissen et al, , 2003Faber et al, 2003]. The histatins are synthesized in the parotid and submandibular glands, meaning that under both stimulated and nonstimulated saliva flow conditions, histatins will be secreted into saliva.…”