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Assessment of pH Responsive Delivery of Methotrexate Based on PHEMA-st-PEG-DA Nanohydrogels

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Abstract

Nanohydrogels (NHs) are novel and attractive carriers for various anticancer factors delivery. The objective of present study is development of a safe NH for pH responsive delivery of methotrexate (MTX). Herein, poly (hydroxyethyl methacrylate) is utilized as the main structure, which is cross-linked with poly(ethyleneglycol) diacrylate (PEG-DA) through reversible addition fragmentation chain transfer polymerization technique. After synthesis, the developed structure is characterized using different methods, including 1H NMR, FT-IR, size exclusion chromatography, transmission electron microscopy and dynamic light scattering. The results confirm successful synthesis of the NH with acceptable yield and nano scale mean size of 194 nm. Methotrexate is conjugated with the aforementioned structure through pH responsive esteric bond. The efficiency of the prepared NH in loading and release of the anticancer drug, methotrexate, is tested. The developed NH shows great potential in methotrexate loading, as well as a faster release rate of methotrexate in acidic pH. The results of in vitro toxicity assessment on MCF-7 as a breast cancer cell line reveal an improved cytotoxicity induction by the methotrexate loaded particles when compared with the free MTX molecules. The suitable size (<200 nm), great potential in loading and release of the methotrexate and cytotoxicity induction in cancer cells are the reliable features of NH as an ideal anti-cancer vehicle.

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References

  1. F. Farjadian, A. Ghasemi, O. Gohari, A. Roointan, M. Karimi, M. R. Hamblin, Nanomedicine, 14, 93 (2018).

    Article  Google Scholar 

  2. F. Farjadian, M. Moghoofei, S. Mirkiani, A. Ghasemi, N. Rabiee, S. Hadifar, A. Beyzavi, M. Karimi, and M. R. Hamblin, Biotechnol. Adv., 36, 968 (2018).

    Article  CAS  Google Scholar 

  3. F. Farjadian, A. Roointan, S. Mohammadi-Samani, and M. Hosseini, Chem. Eng. J., 359, 684 (2018).

    Article  Google Scholar 

  4. M. Hosseini, F. Farjadian, and A. S. H. Makhlouf, in Industrial Applications/or Intelligent Polymers and Coatings, Springer, 2016, pp 1–26.

  5. A. Roointan, S. Kianpour, F. Memari, M. Gandomani, S. M. Gheibi Hayat, and S. Mohammadi-Samani, J. Polym. Mater. Polym. Biomater.., 67, 1028 (2018).

    Article  CAS  Google Scholar 

  6. O. Erol, A. Pantula, W. Liu, and D. H. Gracias, Adv. Mater. Technol., 4, 1900043 (2019).

    Article  Google Scholar 

  7. M. Akram and R. Hussain, in Nanocellulose and Nanohydrogel Matrices: Biotechnological and Biomedical Applications, 2017, pp 297–330.

  8. P. K. Bolla, V. A. Rodriguez, R. S. Kalhapure, and J. Renukuntla, J. Drug Deliv. Sci. Technol., 46, 416 (2018).

    Article  CAS  Google Scholar 

  9. B. Massoumi, Z. Mozaffari, M. Jaymand, Int. J. Biol. Macromol., 117, 418 (2018).

    Article  CAS  Google Scholar 

  10. M. Rizwan, R. Yahya, A. Hassan, M. Yar, A. Azzahari, V. Selvanathan, F. Sonsudin, and C. Abouloula, Polymers, 9, 137 (2017).

    Article  Google Scholar 

  11. J. Li and D. J. Mooney, Nature Reviews Materials, 1, 1 (2016).

    Google Scholar 

  12. S. S. Mishra and A. K. Sharma, Pharma Innovation J., 7, 182 (2018).

    CAS  Google Scholar 

  13. H. Gangadharappa, S. M. C. Prasad, R. P. Singh, J. Drug Deliv. Sci. Technol., 41, 488 (2017).

    Article  CAS  Google Scholar 

  14. W.-F. Lai and Z.-D. He, J. Control. Release, 243, 269 (2016).

    Article  CAS  Google Scholar 

  15. G. Moad, Polym. Chem., 8, 177 (2017).

    Article  CAS  Google Scholar 

  16. F. Farjadian, S. Schwark, and M. Ulbricht, Polym. Chem., 6, 1584 (2015).

    Article  CAS  Google Scholar 

  17. C. N. Kotanen, D. R. Janagam, R. Idziak, L. Rhym, R. Sullivan, A. M. Wilson, T. L. Lowe, and A. Guiseppi-Elie, Europ. Polym. J., 72, 438 (2015).

    Article  CAS  Google Scholar 

  18. A. Bhat, B. Smith, C.-Z. Dinu, and A. Guiseppi-Elie, Mater. Sci. Eng. C, 98, 89 (2019).

    Article  CAS  Google Scholar 

  19. S. Gatti, A. Agostini, R. Ferrari, and D. Moscatelli, Polymers, 9, 389 (2017).

    Article  Google Scholar 

  20. G. Choi, T.-H. Kim, J.-M. Oh, and J.-H. Choy, Coord. Chem. Rev., 359, 32 (2018).

    Article  CAS  Google Scholar 

  21. S. Davaran, H. Fazeli, A. Ghamkhari, F. Rahimi, O. Molavi, M. Anzabi, and R. Salehi, J. Biomater. Sci., Polym. Ed., 29, 1265 (2018).

    Article  CAS  Google Scholar 

  22. F. Farjadian, S. Ghasemi, and S. Mohammadi-Samani, Int. J. Pharm., 504, 110 (2016).

    Article  CAS  Google Scholar 

  23. C. de Oliveira, S. Büttenbender, W. Prado, A. Beckenkamp, A. Asbahr, A. Buffon, S. Guterres, and A. Pohlmann, Nanomaterials, 8, 24 (2018).

    Article  Google Scholar 

  24. N. Silva, A. Riveros, N. Yutronic, E. Lang, B. Chornik, S. Guerrero, J. Samitier, P. Jara, and M. Kogan, Nanomaterials, 8, 985 (2018).

    Article  Google Scholar 

  25. J. Zhao, M. Zhao, C. Yu, X. Zhang, J. Liu, X. Cheng, R. J. Lee, F. Sun, L. Teng, and Y. Li, Int. J. Nanomedicine, 12, 6735 (2017).

    Article  CAS  Google Scholar 

  26. J. Xie, Z. Fan, Y. Li, Y. Zhang, F. Yu, G. Su, L. Xie, and Z. Hou, Int. J. Nanomedicine, 13, 1381 (2018).

    Article  CAS  Google Scholar 

  27. A. Roointan, J. Farzanfar, S. Mohammadi-Samani, A. Behzad-Behbahani, and F. Farjadian, Int. J. Pharm., 552, 301 (2018).

    Article  CAS  Google Scholar 

  28. F. Farjadian, S. Ghasemi, Z. Andami, and B. Tamami, Iranian Polym. J., 29, 197 (2020).

    Article  CAS  Google Scholar 

  29. F. Farjadian, S. Rezaeifard, M. Naeimi, S. Ghasemi, S. Mohammadi-Samani, M. E. Welland, and L. Tayebi, Int. J. Nanomedicine, 14, 6901 (2019).

    Article  CAS  Google Scholar 

  30. S. Ghasemi and Z. A. Harandi, RSC Adv., 8, 14570 (2018).

    Article  CAS  Google Scholar 

  31. S. B. Perrier, Macromolecules, 50, 7433 (2017).

    Article  CAS  Google Scholar 

  32. J. Farzanfar and A. R. Rezvani, Res. Chem. Int., 41, 8975 (2015).

    Article  CAS  Google Scholar 

  33. Q. Xu, A. Sigen, Y. Gao, L. Guo, J. Creagh-Flynn, D. Zhou, U. Greiser, Y. Dong, F. Wang, and H. Tai, Acta Biomater., 75, 63 (2018).

    Article  CAS  Google Scholar 

  34. D. Rosenblum, N. Joshi, W. Tao, J. M. Karp, and D. Peer, Nat. Commun., 9, 1410 (2018).

    Article  Google Scholar 

  35. J. Kydd, R. Jadia, P. Velpurisiva, A. Gad, S. Paliwal, and P. Rai, Pharmaceutics, 9, 46 (2017).

    Article  Google Scholar 

  36. S. K. Golombek, J.-N. May, B. Theek, L. Appold, N. Drude, F. Kiessling, and T. Lammers, Adv. Drug Deliv. Rev., 130, 17 (2018).

    Article  CAS  Google Scholar 

  37. S. Mohammadi-Samani, S. Zojaji, and E. Entezar-Almahdi, J. Drug Deliv. Sci. Technol., 47, 427 (2018).

    Article  CAS  Google Scholar 

  38. J. Chen, X. Yang, L. Huang, H. Lai, C. Gan, and X. Luo, Drug Deliv., 25, 1932 (2018).

    Article  CAS  Google Scholar 

  39. C. Schwall and I. Banerjee, Materials, 2, 577 (2009).

    Article  CAS  Google Scholar 

  40. N. Kohler, C. Sun, J. Wang, and M. Zhang, Langmuir, 21, 8858 (2005).

    Article  CAS  Google Scholar 

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Acknowledgments

The supports of present work from Shiraz University of Medical Sciences — Iran (Grant No. 95-01-36-11579) and Iran National Science Foundation (Grant No. 97007686) is highly acknowledged. The authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript.

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Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Javad Farzanfar, Fatemeh Farjadian & Soliman Mohammadi-Samani

  2. Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Javad Farzanfar & Soliman Mohammadi-Samani

  3. Regenerative Medicine Research Center (RMRC), Isfahan University of Medical Sciences, Isfahan, Iran

    Amir Roointan

  4. School of Dentistry, Marquette University, Milwaukee, USA

    Lobat Tayebi

Authors
  1. Javad Farzanfar
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  2. Fatemeh Farjadian
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  3. Amir Roointan
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  4. Soliman Mohammadi-Samani
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  5. Lobat Tayebi
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Correspondence to Fatemeh Farjadian or Soliman Mohammadi-Samani.

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Farzanfar, J., Farjadian, F., Roointan, A. et al. Assessment of pH Responsive Delivery of Methotrexate Based on PHEMA-st-PEG-DA Nanohydrogels. Macromol. Res. 29, 54–61 (2021). https://doi.org/10.1007/s13233-021-9007-6

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  • DOI: https://doi.org/10.1007/s13233-021-9007-6

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