Synthetic decapeptide reduces bacterial load and accelerates healing in the wounds of restraint-stressed mice

Richard L. Williams, Herve Y. Sroussi, Johnathan J. Abercrombie, Kai Leung, Phillip Marucha

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Wound healing is a complex process involving four transitional yet concurrent stages: coagulation, inflammation, cell proliferation/epithelialization and remodeling. These overlapping stages occur uneventfully in normal physiology. However, during psychological stress, the inflammatory response can become dysregulated and result in increased susceptibility to bacterial infection and delayed wound closure. In our restraint stress model, cutaneous wounds of stressed SKH-1 mice demonstrate significantly higher levels of bacterial load, and healing progresses at a rate 30% slower, than in non-stressed mice. The purpose of this study was to test the hypothesis that a synthetic antimicrobial decapeptide (KSLW) enhances bacterial clearance during stress-impaired healing in mice. Here, using a Pluronic block copolymer nanocarrier, we endeavored to identify an efficient drug delivery system for KSLW, which would enhance the stability, substantivity and function of the cationic peptide in delayed-healing wounds. In this study, intradermal treatment of excisional wounds of stressed mice with 2. mg/ml KSLW loaded in Pluronic F68, resulted in a sustained antimicrobial effect through post-operative day 5, with a 2-log (p<0.01) reduction in bacterial load compared with other stressed mice. The demonstrated bacterial reduction in KSLW-treated stressed mice did not approach the levels observed among control mice. Furthermore, treatment of stressed mice with KSLW improved healing, resulting in significantly faster (p<0.05) wound closure from days 2 to 5 post-wounding, relative to untreated stressed mice and stressed mice treated with Pluronic alone. These findings suggest that Pluronic F68 is an efficient carrier for KSLW, which improves its stability and activity in impaired dermal wounds.

Original languageEnglish (US)
Pages (from-to)588-596
Number of pages9
JournalBrain, Behavior, and Immunity
Volume26
Issue number4
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Bacterial Load
Wound Healing
Poloxamer
Wounds and Injuries
Skin
Drug Delivery Systems
Psychological Stress
Bacterial Infections
Cell Proliferation
Inflammation
Peptides

Keywords

  • Antimicrobial peptide
  • Bacterial clearance
  • Drug delivery
  • Inflammation
  • Nanocarrier
  • Toll-like receptor-4
  • Tri-block copolymer
  • Wound healing

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Synthetic decapeptide reduces bacterial load and accelerates healing in the wounds of restraint-stressed mice. / Williams, Richard L.; Sroussi, Herve Y.; Abercrombie, Johnathan J.; Leung, Kai; Marucha, Phillip.

In: Brain, Behavior, and Immunity, Vol. 26, No. 4, 05.2012, p. 588-596.

Research output: Contribution to journalArticle

Williams, Richard L. ; Sroussi, Herve Y. ; Abercrombie, Johnathan J. ; Leung, Kai ; Marucha, Phillip. / Synthetic decapeptide reduces bacterial load and accelerates healing in the wounds of restraint-stressed mice. In: Brain, Behavior, and Immunity. 2012 ; Vol. 26, No. 4. pp. 588-596.
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