title: Synthetic decapeptide reduces bacterial load and accelerates healing in the wounds of restraint-stressed mice.
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 2mg/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.
authors.affiliation: Dental and Trauma Research Detachment, US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA. richard.williams15@amedd.army.mil
authors.forename: Richard L
authors.initials: RL
authors.lastname: Williams
authors.forename: Herve Y
authors.initials: HY
authors.lastname: Sroussi
authors.forename: Johnathan J
authors.initials: JJ
authors.lastname: Abercrombie
authors.forename: Kai
authors.initials: K
authors.lastname: Leung
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Marucha
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D058491:Bacterial Load / Q000187:drug effects*; D005260:Female; D007249:Inflammation; D051379:Mice; D008812:Mice, Hairless; D012149:Restraint, Physical; D012867:Skin / Q000293:injuries; D013315:Stress, Psychological; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D023181:Antimicrobial Cationic Peptides; C554541:lysyl-lysyl-valyl-valyl-phenylalanyl-tryptophyl-valyl-lysyl-phenylalanyl-lysine