Controlled Release of LL‐37‐Derived Synthetic Antimicrobial and Anti‐Biofilm Peptides SAAP‐145 and SAAP‐276 Prevents Experimental Biomaterial‐Associated Staphylococcus aureus Infection

• Published in: Advanced functional materials 2017-05, Vol.27 (20), p.n/a
• Main Authors: Riool, Martijn, de Breij, Anna, de Boer, Leonie, Kwakman, Paulus H. S., Cordfunke, Robert A., Cohen, Or, Malanovic, Nermina, Emanuel, Noam, Lohner, Karl, Drijfhout, Jan W., Nibbering, Peter H., Zaat, Sebastian A. J.
• Format: Article
• Language: English
• Subjects: antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; antimicrobial peptides; Bacteria; Biofilms; biomaterial‐associated infections; Coating effects; Controlled release; controlled release coatings; Encapsulation; Materials science; MDR Staphylococcus aureus; Mice; Pathogens; Penicillin; Peptides; Surgical implants; Transplants & implants
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201606623

The present study aims to develop an implant coating releasing novel antimicrobial agents to prevent biomaterial‐associated infections. The LL‐37‐derived synthetic antimicrobial and anti‐biofilm peptides (SAAP)‐145 and SAAP‐276 exhibit potent bactericidal and anti‐biofilm activities against clinical and multidrug‐resistant Staphylococcus aureus strains by rapid membrane permeabilization, without inducing resistance. Injection of SAAP‐145, but not SAAP‐276, along subcutaneous implants in mice reduces S. aureus implant colonization by approximately 2 log, but does not reduce bacterial numbers in surrounding tissue. To improve their efficacy, SAAP‐145 and SAAP‐276 are incorporated in a polymer–lipid encapsulation matrix (PLEX) coating, providing a constant release of 0.6% daily up to 30 d after an initial burst release of >50%. In a murine model for biomaterial‐associated infection, SAAP‐145‐PLEX and SAAP‐276‐PLEX coatings significantly reduce the number of culture positive implants and show ≥3.5 and ≥1.5 log lower S. aureus implant and tissue colonization, respectively. Interestingly, these peptide coatings are also highly effective against multidrug‐resistant S. aureus, both reducing implant colonization by ≥2 log. SAAP‐276‐PLEX additionally reduces tissue colonization by 1 log. Together, the peptide‐releasing PLEX coatings hold promise for further development as an alternative to coatings releasing conventional antibiotics to prevent biomaterial‐associated infections. The novel synthetic antimicrobial and anti‐biofilm peptides SAAP‐145 and SAAP‐276 releasing in a controlled fashion from a biodegradable polymer–lipid‐based coating on titanium prevent biomaterial‐associated (multi‐drug‐resistant) Staphylococcus aureus infection in mice. These SAAPs exhibit potent bactericidal and anti‐biofilm activities at low micromolar concentrations against clinical and multidrug‐resistant S. aureus strains by rapid membrane permeabilization, without inducing resistance.