Abstract
Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in Deep Tissue Injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy.
Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models.
Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing.
Results: The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than the other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation. In contrast, control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylated-STAT3.
Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.
Keywords: Curcumin, PLGA, nanoparticle, deep tissue injury, wound healing, pressure injury.
Graphical Abstract