Dual thermo- and pH-responsive poly(N-isopropylacrylamide-co-(2-dimethylamino) ethyl methacrylate)-g-PEG nanoparticle system and its potential in controlled drug release

Abstract

Stimulus-responsive nanoparticles have been widely used for many applications in biotechnology and medicine. In this study, dual thermo- and pH-responsive P(NIPAM-co-DMAEMA)-g-PEG nanoparticles has been synthesized by emulsion polymerization. The obtained nanoparticles were characterized by TEM, DLS, UV–Vis, 1HNMR and GPC analytical methods. The P(NIPAM-co-DMAEMA)-g-PEG nanoparticles showed higher LCST than poly(N-isopropylacrylamide) nanoparticles at 45 °C. Swelling and drug release measurements were taken under different conditions. The released amount of methotrexate (MTX) at normal physiological pH and temperature was limited (24%), while an accumulation drug release of about 70% was obtained after 48 h at pH = 5.5 under hyperthermia conditions (45 °C). MTX release data from the prepared nanoparticles were applied to the various conventional kinetic equations. The model with the highest R2 was considered as the best one. MCF-7 cell line was used to evaluate the cytotoxicity of the unloaded and MTX-loaded nanoparticles alone or in combination with hyperthermia. The results showed that the MTX-loaded nanoparticles in combination with hyperthermia suppressed tumor growth efficiently. According to the results, it can be concluded that the prepared nanoparticles might be regarded as promising agents in controlled drug delivery and multimodal cancer therapy to achieve a more effective treatment.

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Acknowledgements

The authors would like to thank the School of Pharmacy, Isfahan University of Medical Science, Isfahan, Iran, for financing this project.

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This article was extracted from the Ph.D. research project of Aylar Najafipour. She performed all the lab experiments by herself. Ali Reza Mahdavian, Hojjat Sadeghi Aliabadia and Afshin Fassihi were the supervisors of the chemistry part of this project.

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Correspondence to Afshin Fassihi.

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Najafipour, A., Mahdavian, A.R., Aliabadi, H.S. et al. Dual thermo- and pH-responsive poly(N-isopropylacrylamide-co-(2-dimethylamino) ethyl methacrylate)-g-PEG nanoparticle system and its potential in controlled drug release. Polym. Bull. 77, 3129–3142 (2020). https://doi.org/10.1007/s00289-019-02895-9

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Keywords

  • Dual responsive
  • NIPAM
  • DMAEMA
  • PEGylation
  • Controlled drug release