TY - JOUR
T1 - Sterically stabilized phospholipid micelles reduce activity of a candidate antimicrobial wound healing adjunct
AU - Williams, Richard L.
AU - Lim, Sok Bee
AU - Onyuksel, Hayat
AU - Marucha, Phillip T.
N1 - Funding Information:
Acknowledgments The authors are grateful to Dr. Kai Leung and Mr. Johnathan Abercrombie, DTRD, for providing the peptide and performing in vitro microbiology assays, respectively. This study was supported by the US Army Medical Research and Materiel Command, Grant #W74SHSQZ6160N548.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Antimicrobial peptide
KW - Drug delivery
KW - Stress
KW - Wound healing
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U2 - 10.1007/s10989-012-9292-1
DO - 10.1007/s10989-012-9292-1
M3 - Article
AN - SCOPUS:84867328074
SN - 1573-3149
VL - 18
SP - 195
EP - 203
JO - Letters in Peptide Science
JF - Letters in Peptide Science
IS - 3
ER -