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Synthesis of thermosensitive nanohydrogels by crosslinker free method based on N-isopropylacrylamide: Applicable in the naltrexone sustained release

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Abstract

A unique and rapid method was used to synthesize thermosensitive self-crosslinked nano (N-isopropylacrylamidevinylpyrrolidone-acrylamide) (NIPAAm-VP-AAm) terpolymers. Nanohydrogels were obtained within 30 min during a polymerization reaction with a convenient yield due to the high dilution of aqueous solution at an elevated temperature. Furthermore, hydrogen peroxide (H2O2) was employed for the first time as a safe initiator without any toxic segments for the thermosensitive polymer synthesis. Different nanohydrogels were obtained by modulating the molar ratio of monomers to initiators and their influences on the composition ratios, thermoresponsive behavior, size distribution, phase separation, and nanohydrogel drug release were investigated. As the synthetic route is crosslinker free, the obtained nanohydrogels can be introduced as a non-toxic efficient drug delivery system (DDS). The possibility of free radical formation on the PNIPAAm chains, which leads to the crosslinked structure, has been investigated theoretically by quantum mechanical calculations. The potential energy surface of the reaction was examined by changing the distance between the OH radical and the H atoms. Considering these calculations, the reaction can proceed from all pathways as it is observed experimentally. The average size of nanohydrogels, as revealed by dynamic light scattering (DLS) and transmission electronic microscopy (TEM), is <50 nm. Finally, naltrexone as an opiate antagonist was selected as a model drug for the investigation of nanohydrogel drug delivery capabilities. Nanohydrogels show sustained naltrexone release beyond 3 months without any initial burst release.

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Authors and Affiliations

  1. Laboratory of Polymer, Faculty of Chemistry, University of Tabriz, Tabriz, Iran

    Marziyeh Fathi & Ali Akbar Entezami

  2. Department of Chemistry, Sistan and Balouchestan University, Zahedan, Iran

    Ali Ebrahimi

  3. Laboratory of Organosilicone, Faculty of Chemistry, University of Tabriz, Tabriz, Iran

    Kazem Dindar Safa

Authors
  1. Marziyeh Fathi
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  2. Ali Akbar Entezami
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  3. Ali Ebrahimi
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  4. Kazem Dindar Safa
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Correspondence to Ali Akbar Entezami.

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Fathi, M., Entezami, A.A., Ebrahimi, A. et al. Synthesis of thermosensitive nanohydrogels by crosslinker free method based on N-isopropylacrylamide: Applicable in the naltrexone sustained release. Macromol. Res. 21, 17–26 (2013). https://doi.org/10.1007/s13233-012-0181-4

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  • DOI: https://doi.org/10.1007/s13233-012-0181-4

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