TY - JOUR
T1 - Controlled Release of LL-37-Derived Synthetic Antimicrobial and Anti-Biofilm Peptides SAAP-145 and SAAP-276 Prevents Experimental Biomaterial-Associated Staphylococcus aureus Infection
AU - Riool, Martijn
AU - de Breij, Anna
AU - de Boer, Leonie
AU - Kwakman, Paulus H. S.
AU - Cordfunke, Robert A.
AU - Cohen, Or
AU - Malanovic, Nermina
AU - Emanuel, Noam
AU - Lohner, Karl
AU - Drijfhout, Jan W.
AU - Nibbering, Peter H.
AU - Zaat, Sebastian A. J.
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.1002/adfm.201606623
DO - https://doi.org/10.1002/adfm.201606623
M3 - Article
SN - 1616-301X
VL - 27
SP - 1606623
JO - Advanced functional materials
JF - Advanced functional materials
IS - 20
ER -