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J Control Release. 2016 Jan 28;222:1-8. doi: 10.1016/j.jconrel.2015.12.003. Epub 2015 Dec 3.

Prevention of Staphylococcus aureus biomaterial-associated infections using a polymer-lipid coating containing the antimicrobial peptide OP-145.

Author information

1
Dept. of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600, RC Leiden, The Netherlands. Electronic address: a.de_breij@lumc.nl.
2
Dept. of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
3
Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600 RC Leiden, the Netherlands.
4
PolyPid Ltd., 18 Hasivim, St. Petach-Tikva 4959376, Israel.
5
Dept. of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600, RC Leiden, The Netherlands.
6
AO Research Institute Davos, AO Foundation, Clavadelerstrasse 8 Davos Platz, CH7270 Davos, Switzerland.

Abstract

The scarcity of current antibiotic-based strategies to prevent biomaterial-associated infections (BAI) and their risk of resistance development prompted us to develop a novel antimicrobial implant-coating to prevent Staphylococcus aureus-induced BAI. We incorporated the antimicrobial peptide OP-145 into a Polymer-Lipid Encapsulation MatriX (PLEX)-coating to obtain high peptide levels for prolonged periods at the implant-tissue interphase. We first confirmed that OP-145 was highly effective in killing S. aureus and inhibiting biofilm formation in vitro. OP-145 injected along S. aureus-inoculated implants in mice significantly reduced the number of culture-positive implants. OP-145 was released from the PLEX coating in a controlled zero-order kinetic rate after an initial 55%-burst release and displayed bactericidal activity in vitro. In a rabbit intramedullary nail-related infection model, 67% of rabbits with PLEX-OP-145-coated nails had culture-negative nails after 28days compared to 29% of rabbits with uncoated nails. In rabbits with PLEX-OP-145-coated nails, bone and soft tissue samples were culture-negative in 67% and 80%, respectively, whereas all bone samples and 71% of the soft tissue samples of rabbits with uncoated nails were infected. Together, PLEX-OP-145 coatings, of which both compounds have already been found safe in man, can prevent implant colonization and S. aureus-induced BAIs.

KEYWORDS:

Antimicrobial coating; Antimicrobial peptides; OP-145; Orthopaedic implant; Rabbit; Staphylococcus aureus

PMID:
26658071
DOI:
10.1016/j.jconrel.2015.12.003
[Indexed for MEDLINE]

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