The impact of the particle size of curcumin nanocarriers and the ethanol on beta_1-integrin overexpression in fibroblasts: A regenerative pharmaceutical approach in skin repair and anti-aging formulations

Daru. 2019 Jun;27(1):159-168. doi: 10.1007/s40199-019-00258-3. Epub 2019 Mar 14.

Abstract

Background: Since women pay more attention to their skin's health, pharmaceutical companies invest heavily on skin care product development. Further, the success of drug nano-carriers in passing through the skin justifies the need to conduct studies at the nano-scale. β1-integrin down regulation has been proposed as a sign of skin aging.

Methods: Six drug nano-carriers (50 and 75 nm) were prepared at three ethanol concentrations (0, 3,and 5%) and different temperatures. Then, the impact of Nanocarriers on fibroblasts were investigated.

Results: DLS showed that increasing ethanol concentration decreased the surface tension that caused a decrease in the particle size in non-temperature formulations while increasing the temperature to 60 °C to lower Gibbs free energy increased the particle size. Ethanol addition decreased β1-integrin over-expression, whereas larger nano-carriers induced an over-expression of β1-integrin, Bcl2/Bax ratio, and an increase in live cell number. β1-integrin over-expression did not correlate with the rate of fibroblast proliferation and NFκB expression. An increase in fibroblast mortality in relation to smaller nano-carriers was not only due to the increase in Bax ratio, but was related to NFκB over-expression.

Conclusion: The development of a regenerative pharmaceutical approach in skin repair was based on the effect of particle size and ethanol concentration of the drug nano-carriers on the expression of β1-integrin in fibroblasts. A curcumin nanoformulation sized 77 nm and containing of 3% ethanol was more effective in increasing β1-integrin gene over-expression, anti-apoptosis of fibroblast cells (Bcl2/Bax ratio), and in decreasing Bax and NFκB gene expression than that with a particle size of 50 nm. Such a formulation may be considered a valuable candidate in anti-aging and wound-healing formulations. Graphical abstract The effect of particle size on Bcl2/Bax ratio and NFκ-B gene expression through the cell surface receptor of ß1- integrin. Bigger nanocarriers induce over-expression of integrin ß1 gene and also lead to an increase in Bcl2/Bax ratio along with a decrease in NFκ-B, unlike the smaller nanocarriers.

Keywords: Nanocarriers; Particle size; Skin aging; Surface tension, chemical stability, integrin β1; Wound healing..

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation
  • Cell Survival / drug effects
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Ethanol / chemistry*
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Integrin beta1 / genetics*
  • Mice
  • NF-kappa B / genetics
  • Nanoparticles
  • Particle Size
  • Skin Aging / drug effects*
  • Up-Regulation*
  • bcl-2-Associated X Protein / genetics

Substances

  • Integrin beta1
  • NF-kappa B
  • bcl-2-Associated X Protein
  • Ethanol
  • Curcumin