Healing Effects of Curcumin Nanoparticles in Deep Tissue Injury Mouse Model.

Abstract

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. 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. CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. 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. 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.