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Controlled Release of LL‐37‐Derived Synthetic Antimicrobial and Anti‐Biofilm Peptides SAAP‐145 and SAAP‐276 Prevents Experimental Biomaterial‐Associated Staphylococcus aureus Infection
Author(s) -
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.
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201606623
Subject(s) - biomaterial , staphylococcus aureus , biofilm , antimicrobial , microbiology and biotechnology , antimicrobial peptides , antibiotics , materials science , biology , bacteria , nanotechnology , genetics
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.