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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

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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.

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.

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Data availability

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References

  1. Hoveizi E, Khodadadi S, Tavakol S, Karima O, Nasiri-Khalili MA. Small molecules differentiate definitive endoderm from human induced pluripotent stem cells on PCL scaffold. Appl Biochem Biotechnol. 2014;173(7):1727–36.

    Article  CAS  PubMed  Google Scholar 

  2. Hoveizi E, Ebrahimi-Barough S, Tavakol S, Sanamiri K. In vitro differentiation of human iPS cells into neural like cells on a biomimetic polyurea. Mol Neurobiol. 2017;54(1):601–7.

    Article  CAS  PubMed  Google Scholar 

  3. Weiss RA. Autologous cell therapy. Facial Plastic Surgery Clinics. 2013;21(2):299–304.

    Article  PubMed  Google Scholar 

  4. Thangapazham RL, Darling TN, Meyerle J. Alteration of skin properties with autologous dermal fibroblasts. Int J Mol Sci. 2014;15(5):8407–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Banerjee R. Overcoming the stratum corneum barrier: a nano approach. Drug delivery and translational research. 2013;3(3):205–8.

    Article  PubMed  Google Scholar 

  6. Sikora E, Bielak-Zmijewska A, Mosieniak G, Piwocka K. The promise of slow down ageing may come from curcumin. Curr Pharm Des. 2010;16(7):884–92.

    Article  CAS  PubMed  Google Scholar 

  7. Shen LR, Parnell LD, Ordovas JM, Lai CQ. Curcumin and aging. Biofactors. 2013;39(1):133–40.

    Article  CAS  PubMed  Google Scholar 

  8. Bala K, Tripathy B, Sharma D. Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology. 2006;7(2):81–9.

    Article  CAS  PubMed  Google Scholar 

  9. Thangapazham RL, Sharad S, Maheshwari RK. Skin regenerative potentials of curcumin. Biofactors. 2013;39(1):141–9.

    Article  CAS  PubMed  Google Scholar 

  10. Giangreco A, Goldie SJ, Failla V, Saintigny G, Watt FM. Human skin aging is associated with reduced expression of the stem cell markers beta 1 integrin and MCSP. J Invest Dermatol. 2010;130(2):604–8.

    Article  CAS  PubMed  Google Scholar 

  11. Raghavan S, Bauer C, Mundschau G, Li Q, Fuchs E. Conditional ablation of β1 integrin in skin. J Cell Biol. 2000;150(5):1149–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Liu S, Shi-Wen X, Blumbach K, Eastwood M, Denton CP, Eckes B, et al. Expression of integrin β1 by fibroblasts is required for tissue repair in vivo. J Cell Sci. 2010;123(21):3674–82.

    Article  CAS  PubMed  Google Scholar 

  13. Rozo M, Li L, Fan C-M. Targeting [beta] 1-integrin signaling enhances regeneration in aged and dystrophic muscle in mice. Nat Med. 2016;22(8):889–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY. Motif module map reveals enforcement of aging by continual NF-κB activity. Genes Dev. 2007;21(24):3244–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD. NF-κB in aging and disease. Aging and disease. 2011;2(6):449–65.

    PubMed  PubMed Central  Google Scholar 

  16. Kriete A, Kari C, Mayo KL, Yalamanchili N, Bender P, Rodeck U, et al. Cell autonomous expression of inflammatory genes in biologically aged fibroblasts associated with elevated NF-kappaB activity. Immun Ageing. 2008;5(1):5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Saengkrit N, Saesoo S, Srinuanchai W, Phunpee S, Ruktanonchai UR. Influence of curcumin-loaded cationic liposome on anticancer activity for cervical cancer therapy. Colloids Surf B: Biointerfaces. 2014;114:349–56.

    Article  CAS  PubMed  Google Scholar 

  18. Hackley V, Clogston J. Measuring the size of nanoparticles in aqueous media using batch-mode dynamic light scattering. NIST Special Publication. 2007;1200:6.

    Google Scholar 

  19. Sun Z, Guo SS, Fässler R. Integrin-mediated mechanotransduction. J Cell Biol. 2016;215(4):445–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Himesh S, Sharan PS, Mishra K, Govind N, Singhai A. Qualitative and quantitative profile of curcumin from ethanolic extract of Curcuma longa. Int Res J Pharm. 2011;2(4):180–4.

    Google Scholar 

  21. Tavakol S, Saber R, Hoveizi E, Aligholi H, Ai J, Rezayat SM. Chimeric self-assembling nanofiber containing bone marrow homing peptide’s motif induces motor neuron recovery in animal model of chronic spinal cord injury; an in vitro and in vivo investigation. Mol Neurobiol. 2016;53(5):3298–308.

    Article  CAS  PubMed  Google Scholar 

  22. Tavakol S, Jalili-Firoozinezhad S, Mashinchian O, Mahmoudi M. Bioinspired nanotechnologies for skin regeneration. Nanoscience in Dermatology. Elsevier. 2016:337–52.

  23. Tavakol S, Nikpour MR, Hoveizi E, Tavakol B, Rezayat SM, Adabi M, et al. Investigating the effects of particle size and chemical structure on cytotoxicity and bacteriostatic potential of nano hydroxyapatite/chitosan/silica and nano hydroxyapatite/chitosan/silver; as antibacterial bone substitutes. J Nanopart Res. 2014;16(10):2622.

    Article  CAS  Google Scholar 

  24. Tavakol S, Kashani IR, Azami M, Khoshzaban A, Tavakol B, Kharrazi S, et al. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM. J Nanopart Res. 2012;14(12):1265.

    Article  CAS  Google Scholar 

  25. Tavakol S, Mousavi SMM, Tavakol B, Hoveizi E, Ai J, Sorkhabadi SMR. Mechano-transduction signals derived from self-assembling peptide nanofibers containing long motif of laminin influence neurogenesis in in-vitro and in-vivo. Mol Neurobiol. 2017;54(4):2483–96.

    Article  CAS  PubMed  Google Scholar 

  26. Tavakol S, Saber R, Hoveizi E, Tavakol B, Aligholi H, Ai J, et al. Self-assembling peptide nanofiber containing long motif of laminin induces neural differentiation, tubulin polymerization, and neurogenesis: in vitro, ex vivo, and in vivo studies. Mol Neurobiol. 2016;53(8):5288–99.

    Article  CAS  PubMed  Google Scholar 

  27. Chin SF, Azman A, Pang SC. Size controlled synthesis of starch nanoparticles by a microemulsion method. J Nanomater. 2014;2014:9.

    Google Scholar 

  28. Salamanca M, Sirignano M, Commodo M, Minutolo P, D’Anna, A. The ethanol effect on particle size distributions in ethylene premixed flame.

  29. Qu Y, Yang H, Yang N, Fan Y, Zhu H, Zou G. The effect of reaction temperature on the particle size, structure and magnetic properties of coprecipitated CoFe 2 O 4 nanoparticles. Mater Lett. 2006;60(29):3548–52.

    Article  CAS  Google Scholar 

  30. Brockbank E, Bridges J, Marshall C, Sahai E. Integrin β1 is required for the invasive behaviour but not proliferation of squamous cell carcinoma cells in vivo. Br J Cancer. 2005;92(1):102–12.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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

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Authors and Affiliations

  1. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Shima Tavakol

  2. Pharmaceutical Sciences Research Center, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran

    Samaneh Zare

  3. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Elham Hoveizi

  4. School of Medicine, Kashan University of Medical Sciences, Isfahan, Iran

    Behnaz Tavakol

  5. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mahdi Rezayat

  6. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mahdi Rezayat

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  1. Shima Tavakol
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Tavakol, S., Zare, S., Hoveizi, E. et al. 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 J Pharm Sci 27, 159–168 (2019). https://doi.org/10.1007/s40199-019-00258-3

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  • DOI: https://doi.org/10.1007/s40199-019-00258-3

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