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Development of thermo/redox-responsive diselenide linked methoxy poly (ethylene glycol)-block-poly(ε-caprolactone-co-p-dioxanone) hydrogel for localized control drug release

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Abstract

Thermo/redox-sensitive injectable hydrogels made from diselenide linked methoxy poly (ethylene glycol)-block-poly (ε-caprolactone-co-p-dioxanone) (Bi(PPCD)-Se2) were reported in this study. Bi(PPCD)-Se2 hydrogels' in vitro degradation characteristics, rheological properties, and sol–gel transition pathways were investigated. The hydrogel has a pronounced viscosity (45 Pa. S), as determined by the rheological results. The Bi(PPCD)-Se2 solution remained in a free-flowing state at low temperatures owing to its amphiphilic behavior, but when heated to physiologic temperatures, it spontaneously changed into a semisolid hydrogel, which is essential for sustained drug release. The temperature of the phase change was discovered to be sensitive on the amount of solvent in the copolymer. Most significantly, the inclusion of diselenide linkages allowed the thermosensitive hydrogels to withstand oxidation and reduction-induced degradation. As a consequence, Bi(PPCD)-Se2 hydrogel degradation was greatly enhanced. This excellent stimuli-responsive DOX-loaded hydrogel has a loading content of 1.3% DOX and an encapsulation efficiency of 93%. For 22 days of incubation at 37 °C with GSH and H2O2 stimuli at pH 7.4, the DOX/Bi (PPCD)-Se2 hydrogel released 81.6% and 85.4% of their payload, respectively. The Bi(PPCD)-Se2 copolymer is biocompatible, according to the MTT experiment, which found no toxicity in HeLa and HaCaT cells. DOX/hydrogel action, on the other hand, resulted in 31.3 ± 2.2% of cell viability in the maximum concentration 10 µg/mL HeLa cells. The produced Bi(PPCD)-Se2 hydrogel could be exploited as a possible drug delivery biomaterial aimed at local drug distribution in a sustained manner due to its good redox triggered degradability.

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Acknowledgements

The authors would like to thank for the financial support from Taiwan's Ministry of Science and Technology.

Funding

The Ministry of Science and Technology of Taiwan financed this research [grant numbers (MOST105-2221-E-011–133-MY3 and 105–2221-E011-151-MY3)].

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Authors and Affiliations

  1. Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, ROC

    Hailemichael Tegenu Gebrie, Kefyalew Dagnew Addisu, Haile Fentahun Darge, Tefera Worku Mekonnen & Hsieh-Chih Tsai

  2. Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, ROC

    Hsieh-Chih Tsai

  3. R&D Center for Membrane Technology, Chung Yuan Christian University, Taoyuan 320, Chungli, Taiwan, ROC

    Hsieh-Chih Tsai

  4. Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, ROC

    Darieo Thankachan kottackal

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  1. Hailemichael Tegenu Gebrie
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Conceptualization: [Hailemichael Tegenu Gebrie, Hsieh-Chih Tsai]; Methodology: [Hailemichael Tegenu Gebrie, Kefyalew Dagnew Addisu, Haile Fentahun Darge]; Formal analysis and investigation: [Hailemichael Tegenu Gebrie, Kefyalew Dagnew Addisu, Tefera Worku Mekonnen]; Writing—original draft preparation: [Hailemichael Tegenu Gebrie, Darieo Thankachan kottackal]; Writing—review and editing: [Hailemichael Tegenu Gebrie, Kefyalew Dagnew Addisu, Tefera Worku Mekonnen]; Funding acquisition: [Hsieh-Chih Tsai]; Resources: [Hsieh-Chih Tsai]; Supervision: [Hsieh-Chih Tsai]. All authors read and approved the final version of the manuscript.

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Gebrie, H.T., Addisu, K.D., Darge, H.F. et al. Development of thermo/redox-responsive diselenide linked methoxy poly (ethylene glycol)-block-poly(ε-caprolactone-co-p-dioxanone) hydrogel for localized control drug release. J Polym Res 28, 448 (2021). https://doi.org/10.1007/s10965-021-02776-8

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