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Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

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Abstract

Recurrent oral ulcer is a painful oral mucosal disorder that affects 20% of the world’s population. The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments. This work reports a hyaluronic acid-based dissolvable microneedle patch (ROUMN patch, short for recurrent oral ulcer microneedle) loaded with dexamethasone acetate, vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers. The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C. In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) expression than dexamethasone alone. Cell proliferation and migration were also significantly promoted by ROUMN compared to vitamin C alone. The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats. ROUMN as a treatment accelerated the healing process of oral ulcers, shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost, a commonly used over-the-counter (OTC) drug for oral ulcers. The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 62003023, 32071407, 52073138, 52003018 and 52003019), Beijing Natural Science Foundation (No. 7212204), and Beijing Advanced Innovation Center for Biomedical Engineering and Beihang University.

Author information

Author notes

  1. Yuqiong Wang, An’an Sheng, Xinran Jiang, and Shanshan Yang have contributed equally to this work.

Authors and Affiliations

  1. Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China

    Yuqiong Wang, An’an Sheng, Xinran Jiang, Shanshan Yang, Long Lin & Lingqian Chang

  2. Department of Stomatology, Xiang’an Hospital of Xiamen University, Xiamen, 361000, China

    An’an Sheng, Shanshan Yang & Jian Li

  3. Institute of Plastic Machinery and Plastic Engineering, School of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing, 100029, China

    Long Lin

  4. Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College, Beijing, 100005, China

    Mingzhu Yang

  5. Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai, 200011, China

    Fengshuo Zhu

  6. Laboratory Animal Facility, Peking University First Hospital, Beijing, 100034, China

    Yongyan Hu

Authors
  1. Yuqiong Wang
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Contributions

LQC and JL conceived the project, collected funding, and guided the experiments. YYH guided the animal experiments. YQW designed the experiments and provided guidance for the study. Microneedle design and fabrication were done by AAS. In vitro experiments and data collection were done by AAS and XRJ. In vivo experiments and data collection were done by YQW and SSY. Manuscript composition and revision were done by YQW and XRJ. LL, MZY and FSZ helped with some experiments.

Corresponding authors

Correspondence to Yongyan Hu, Jian Li or Lingqian Chang.

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Conflict of interest

The authors declare that there is no conflict of interest.

Ethical approval

This project was approved by Xiamen University Animal Care and Use Committee. The approval code number is XMULAC20210063. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Wang, Y., Sheng, A., Jiang, X. et al. Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer. Bio-des. Manuf. 6, 255–267 (2023). https://doi.org/10.1007/s42242-022-00221-3

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  • DOI: https://doi.org/10.1007/s42242-022-00221-3

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