Antimicrobial peptides (AMPs) are good candidates to treat
burn wounds, a major cause of morbidity, impaired life quality and resources consumption in developed countries. We took advantage of a commercially available
hydrogel, Carbopol®, a vehicle for
topical administration that maintains a moist environment within the
wound site. We hypothesized that the incorporation of
LLKKK18 conjugated to
dextrin would improve the healing process in rat
burns. Whereas the
hydrogel improves healing,
LLKKK18 released from the
dextrin conjugates further accelerated
wound closure, and simultaneously improving the quality of healing. Indeed, the release of
LLKKK18 reduced oxidative stress and
inflammation (low neutrophil and macrophage infiltration and pro-inflammatory
cytokines levels). Importantly, it induced a faster resolution of the inflammatory stage through early M2 macrophage recruitment. In addition,
LLKKK18 stimulated angiogenesis (increased
VEGF and microvessel development in vivo). Moreover,
collagen staining evaluated by Masson's Trichrome was visually much more intense
after treatment with
LLKKK18, suggesting higher
collagen deposition. Overall, we generated an effective, safe and inexpensive formulation that maintains a moist environment in the
wound, easy to apply and remove, and with potential to prevent
infection due to the presence of an
antimicrobial peptide. These findings propel us to further study this LLKKK18-containing formulation, setting the foundations towards a potential therapeutic approach for
burn wound treatment.
STATEMENT OF SIGNIFICANCE: This work presents a newly developed formulation that holds great potential as a therapeutic approach for
burn treatment. It is based on the sustained delivery of an
antimicrobial peptide -
LLKKK18 - from conjugates with
dextrin, after degradation of
dextrin backbone upon exposure to
wound α-
amylases. Conjugates were further embedded in Carbopol®, a commercially available
hydrogel, suitable for
topical administration and that provides a moist environment to the
wound. Overall, we obtained an efficient, safe and non-expensive formulation that improves
burn wound healing, maintains a moist environment within the
wound, is easy to apply-and-remove, and has potential to prevent
infection due to the presence of an
antimicrobial peptide. Importantly, this is the first time the wound healing ability of
LLKKK18 is demonstrated and that its main mechanisms of action are identified.