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

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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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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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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Keywords

  • RAFT synthesis
  • nanohydrogel
  • PHEMA
  • PEG-DA
  • methotrexate
  • drug delivery
  • cancer.