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

• Published in: Journal of controlled release Vol. 222; pp. 1 - 8
• Main Authors: de Breij, A., Riool, M., Kwakman, P.H.S., de Boer, L., Cordfunke, R.A., Drijfhout, J.W., Cohen, O., Emanuel, N., Zaat, S.A.J., Nibbering, P.H., Moriarty, T.F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.01.2016
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antimicrobial Cationic Peptides - administration & dosage; Antimicrobial Cationic Peptides - therapeutic use; Antimicrobial coating; Antimicrobial peptides; Biofilms; Cholesterol - chemistry; Female; Lactic Acid - chemistry; Mice, Inbred C57BL; Nail Diseases - drug therapy; OP-145; Orthopaedic implant; Phosphatidylcholines - chemistry; Polyglycolic Acid - chemistry; Prostheses and Implants; Rabbit; Rabbits; Silicones - chemistry; Staphylococcal Infections - prevention & control; Staphylococcus aureus; Staphylococcus aureus - drug effects; Orthopaedic implant; Rabbit; Antimicrobial coating; OP-145; Staphylococcus aureus; Antimicrobial peptides
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2015.12.003

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. [Display omitted]