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.

Abstract

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. Six drug nano-carriers (50 and 75nm) were prepared at three ethanol concentrations (0, 3,and 5%) and different temperatures. Then, the impact of Nanocarriers on fibroblasts were investigated. 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. 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 77nm 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 50nm. 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.