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

  • Shima Tavakol
  • Samaneh Zare
  • Elham Hoveizi
  • Behnaz Tavakol
  • Seyed Mahdi Rezayat
Research Article



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 75 nm) 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 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.


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



This work was supported by grant from “Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran (grant number 94-05-118-27255)”.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran
  2. 2.Pharmaceutical Sciences Research Center, Pharmaceutical Sciences BranchIslamic Azad University (IAUPS)TehranIran
  3. 3.Department of Biology, Faculty of ScienceShahid Chamran University of AhvazAhvazIran
  4. 4.School of MedicineKashan University of Medical SciencesIsfahanIran
  5. 5.Department of Medical Nanotechnology, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  6. 6.Department of Pharmacology, School of MedicineTehran University of Medical SciencesTehranIran

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