Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China; Division of Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.
Biomaterials. 2025 Mar;314:122908. doi: 10.1016/j.biomaterials.2024.122908. Epub 2024 Oct 21.
Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.
真菌感染影响全球超过 1300 万人，并导致每年 150 万人死亡。一些深部皮肤真菌感染可能会扩展皮肤屏障，导致全身感染，从而导致严重的发病率和死亡率。然而，深部皮肤真菌感染的治疗具有挑战性，传统治疗方法往往忽略了这一点，因为这些方法只能在深部组织中提供有限的药物。在这项研究中，我们开发了一种电刺激微针贴片，将咪康唑递送至皮下层。我们使用模拟真菌感染的体外和离体模型来测试其抗真菌功效。此外，我们在小鼠皮下真菌感染模型中证实了其抗真菌和伤口愈合作用。此外，我们的研究结果还表明，咪康唑和施加电流的组合协同刺激伤害感受感觉神经，从而激活由真皮树突状细胞和 γδ-T 细胞介导的保护性皮肤免疫。总的来说，这项研究为深部组织中治疗剂的微创递送和神经-免疫轴的调节提供了一种新策略。
