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Flurbiprofen microneedle patches for the management of acute postoperative pain

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Abstract

Acute postoperative pain is commonly treated with flurbiprofen (FBP), but conventional delivery methods are suboptimal. This study prepared a new non-burst release microneedles (MNs) using genipin cross-linked gelatin (cGel). By adding varying amounts of genipin to modulate the crosslinking degree of cGel, the drug release behavior of the drug-loaded MNs in the skin can be altered. The crosslinking parameters that meet therapeutic requirements are selected, thus providing rapid and long-lasting analgesic effects. cGel solutions were successfully cross-linked, altering matrix material microstructure, confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy. MNs demonstrated increasing mechanical strength with higher crosslinking. Drug release rates were rapid initially, then slowed, exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking. In vivo, FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery, with the greatest effect observed at 2–3 h post-surgery, and can maintain analgesia for up to 6 h. Biosafety tests confirmed good biocompatibility. FBP/cGel MNs effectively penetrate the stratum corneum, safely delivering drugs with significant analgesic effects, excellent mechanical properties, and good biocompatibility, representing a promising strategy for managing acute postoperative pain.

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Acknowledgements

This research was funded by the National Key Research and Development Program of China (Nos. 2022YFB3205602 and 2022YFB3804703), the National Natural Science Foundation of China (Nos. 52372174, 61875015, and T2125003), the Bei**g Natural Science Foundation (Nos. L212046 and L212010), the Fundamental Research Funds for the Central Universities. All animal experiments conducted in this study were reviewed and approved by the Animal Experimentation Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences (Ethical Approval No. NCC2023A291).

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Authors and Affiliations

  1. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei**g, 100021, China

    Huaqing Chu & Hui Zheng

  2. Bei**g Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Bei**g, 101400, China

    Huaqing Chu, Yanyan Zhang, Jiangtao Xue, Cong Li & Zhou Li

  3. Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China

    Yanyan Zhang & Wei Zhang

  4. School of Life Science, Institute of Engineering Medicine, Bei**g Institute of Technology, Bei**g, 100081, China

    Jiangtao Xue

  5. Institute of Process Engineering, Chinese Academy of Sciences, Bei**g, 100190, China

    Yuan Yang

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  1. Huaqing Chu
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  6. Wei Zhang
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Correspondence to Wei Zhang, Zhou Li or Hui Zheng.

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Chu, H., Zhang, Y., Yang, Y. et al. Flurbiprofen microneedle patches for the management of acute postoperative pain. Nano Res. (2024). https://doi.org/10.1007/s12274-024-6751-x

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  • DOI: https://doi.org/10.1007/s12274-024-6751-x

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