期刊
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
卷 18, 期 3, 页码 195-203出版社
SPRINGER
DOI: 10.1007/s10989-012-9292-1
关键词
Antimicrobial peptide; Wound healing; Drug delivery; Stress
资金
- US Army Medical Research and Materiel Command [W74SHSQZ6160N548]
KSLW is an antimicrobial decapeptide, presumed to associate with micelles. Linear polymeric chains of hydrophobic phospholipids tend to form micelles, spontaneously, and function as efficient drug-stabilizing delivery systems. Our goal was to examine whether association of a cationic decapeptide with sterically stabilized nanomicelles (SSMs), improves stability and antimicrobial effect in vivo, using an impaired healing model. KSLW solutions were prepared in either saline or 12 mM SSM. Bilateral circular excisional wounds were created on the backs of SKH-1 mice followed by intradermal delivery of peptide solutions. Bacterial assays were conducted to assess bioactivity of KSLW in different formulations. Fluorescence analyses demonstrated an optimum lipid:peptide ratio for loading KSLW in PEGylated phospholipid micelles to be 15:1. Stressed animals treated with KSLW-SSM preparations demonstrated no differences in microbial load at post-operative time points. In vitro assays against Staphylococcus epidermidis confirmed diminished activity of KSLW in SSM solution. The loss of KSLW antimicrobial activity may be based on electrostatic interactions with the anionic surface of SSM, which interfere with the peptide's interaction with bacterial membranes. This study emphasizes the importance of antimicrobial peptide charge, size, and bioactivity, when designing delivery systems for wound healing agents.
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