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Fabrication of gelatin methacryloyl hydrogel microneedles for transdermal delivery of metformin in diabetic rats

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Abstract

Injection therapy for diabetes has poor patient compliance, and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients. In this work, to demonstrate the benefits of an alternative drug delivery technique that overcomes these issues, methacrylated gelatin hydrogel-forming microneedles integrated with metformin were developed to adjust blood glucose levels in diabetic rats. Gelatin methacryloyl microneedles (GelMA-MNs) with different degrees of substitution were successfully prepared by a micro-molding method. The resultant GelMA-MNs exhibited excellent mechanical properties and moisture resistance. Metformin, an anti-diabetic drug, was further encapsulated into the GelMA-MNs, and its release rate could be controlled by the three-dimensional cross-linked network of microneedles, thereby exhibiting sustained drug release behaviors in vitro and implying a better therapeutic effect compared with that of subcutaneous injection in diabetic rats. The drug release period could be significantly prolonged by improving the cross-link density of GelMA-MNs. The results of hypoglycemic effect evaluation show that the application of GelMA-MNs for transdermal delivery in diabetic rats has promising benefits for diabetes treatment.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 51873194) and the Natural Science Foundation of Zhejiang Province, China (No. LY18E030006). We also gratefully acknowledge Zhejiang Academy of Medical Science for histological experiments.

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Authors and Affiliations

  1. School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Zhiyong Zeng, Guohua Jiang, Tianqi Liu, Gao Song, Xueya Zhang, Yanting Jing, Mingjia Feng & Yufei Shi

  2. Institute of Smart Biomedical Materials, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Guohua Jiang

  3. Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Guohua Jiang

  4. College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Yanfang Sun

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  1. Zhiyong Zeng
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  2. Guohua Jiang
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  3. Tianqi Liu
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  4. Gao Song
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  5. Yanfang Sun
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  7. Yanting Jing
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  9. Yufei Shi
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Contributions

ZYZ and GHJ contributed to conceptualization; ZYZ contributed to the experimental research; GHJ and YF Sun contributed to resources, funding acquisition and supervision; XYZ, GS, and TQL contributed to methodology; ZYZ contributed to writing; YTJ, MJF, and YF Shi helped in animal experimental research and data analysis; GHJ reviewed and edited the manuscript.

Corresponding authors

Correspondence to Guohua Jiang or Yanfang Sun.

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The authors declare that there is no conflict of interest.

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All institutional and national guidelines for the care and use of laboratory animals were followed. All the animal procedures were reviewed and approved by the Animal Ethics Committee of Zhejiang Sci-Tech University (acceptance number: 2019-02-01).

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Zeng, Z., Jiang, G., Liu, T. et al. Fabrication of gelatin methacryloyl hydrogel microneedles for transdermal delivery of metformin in diabetic rats. Bio-des. Manuf. 4, 902–911 (2021). https://doi.org/10.1007/s42242-021-00140-9

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