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Bio-Design and Manufacturing  2023 Vol.6 No.3 P.255-267

http://doi.org/10.1007/s42242-022-00221-3


Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer


Author(s):  Yuqiong Wang, Anan Sheng, Xinran Jiang, Shanshan Yang, Long Lin, Mingzhu Yang, Fengshuo Zhu, Yongyan Hu, Jian Li & Lingqian Chang

Affiliation(s):  Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; more

Corresponding email(s):   huyyg@163.com, riken@xmu.edu.cn, lingqianchang@buaa.edu.cn

Key Words:  Recurrent oral ulcer, Dissolvable microneedle, Hyaluronic acid microneedle, Multidrug, Anti-inflammation, Healing promoting effect


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Yuqiong Wang, Anan Sheng, Xinran Jiang, Shanshan Yang, Long Lin, Mingzhu Yang, Fengshuo Zhu, Yongyan Hu, Jian Li & Lingqian Chang. Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer[J]. Journal of Zhejiang University Science D, 2023, 6(3): 255-267.

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journal="Journal of Zhejiang University Science D",
volume="6",
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pages="255-267",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1007/s42242-022-00221-3"
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Abstract: 
recurrent oral ulcer is a painful oral mucosal disorder that affects 20% of the worlds 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.

北航常凌乾、厦大附属翔安医院李健等 | 用于治疗复发性口腔溃疡的多药联合可溶微针贴片

本研究论文聚焦一种搭载三药联合的透明质酸可溶微针ROUMN,用于治疗复发性口腔溃疡(复发性阿弗他溃疡)。由于复发性口腔溃疡治病机理不明,现有疗法主要聚焦于改善症状、加速愈合。因此,药物的选择通常包括皮质醇、抗菌类、促愈合和镇痛类。然而,以常见的口腔贴片、药膏、喷雾或漱口水形式给药的治疗方式无法确保给药时长,导致治疗效果的削弱。


本研究筛选出固化后针尖成型度高、针体硬度好、微针基底韧性强的300 kDa透明质酸作为基质材料,其所制成的微针在刺入皮肤后10秒可完全溶解,且在相同载药量下,总释药量达到明胶/玉米淀粉微针的2倍。根据大鼠口腔溃疡模型订制的350 μm针长可以确保微针刺入溃疡的假性粘膜后直接给药到溃疡底部,在整个溃疡中达到均匀的药物分布。ROUMN采用了醋酸地塞米松、维他命C和盐酸丁卡因的药物组合,使微针贴片在镇痛的同时达到消炎、促愈合的治疗效果。实验表明,三药联合产生的抗炎效果显著高于单独使用地塞米松,对细胞的促增殖和迁移效果也显著高于单独使用维他命C。在对大鼠口腔溃疡模型的治疗中,ROUMN相比于临床常用药西瓜霜粉剂,可将愈合时间从7天缩短至5天。病理切片显示,经ROUMN治疗的口腔溃疡在第一次用药之后即表现出更快的修复速度,在第3天时已完成真皮层的修复,同时炎症反应也显著低于其他组。本研究为治疗复发性口腔溃疡的给药方式和药物组合提供了改善思路,也展示了ROUMN的高转化价值及应用前景。

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