Department of Electrical Engineering, Soongsil University, Seoul 06978, Republic of Korea.
Department of Mechanical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Sci Transl Med. 2019 Jul 31;11(503). doi: 10.1126/scitranslmed.aaw3329.
A flexible microneedle patch that can transdermally deliver liquid-phase therapeutics would enable direct use of existing, approved drugs and vaccines, which are mostly in liquid form, without the need for additional drug solidification, efficacy verification, and subsequent approval. Specialized dissolving or coated microneedle patches that deliver reformulated, solidified therapeutics have made considerable advances; however, microneedles that can deliver liquid drugs and vaccines still remain elusive because of technical limitations. Here, we present a snake fang-inspired microneedle patch that can administer existing liquid formulations to patients in an ultrafast manner (<15 s). Rear-fanged snakes have an intriguing molar with a groove on the surface, which enables rapid and efficient infusion of venom or saliva into prey. Liquid delivery is based on surface tension and capillary action. The microneedle patch uses multiple open groove architectures that emulate the grooved fangs of rear-fanged snakes: Similar to snake fangs, the microneedles can rapidly and efficiently deliver diverse liquid-phase drugs and vaccines in seconds under capillary action with only gentle thumb pressure, without requiring a complex pumping system. Hydrodynamic simulations show that the snake fang-inspired open groove architectures enable rapid capillary force-driven delivery of liquid formulations with varied surface tensions and viscosities. We demonstrate that administration of ovalbumin and influenza virus with the snake fang-inspired microneedle patch induces robust antibody production and protective immune response in guinea pigs and mice.
一种可经皮传递液相治疗剂的柔性微针贴片,将能够直接使用现有的、已批准的药物和疫苗,这些药物和疫苗大多为液态,而无需额外的药物固化、疗效验证和随后的批准。专门的溶解或涂层微针贴片已经在传递重新配方的固化治疗剂方面取得了相当大的进展;然而,由于技术限制,能够传递液态药物和疫苗的微针仍然难以实现。在这里,我们展示了一种受蛇牙启发的微针贴片,它可以以超快的速度 (<15 s) 将现有的液体制剂施用于患者。后齿蛇类有一个有趣的臼齿,表面有一个凹槽,这使其能够快速有效地将毒液或唾液注入猎物体内。液体输送基于表面张力和毛细作用。微针贴片采用了多种开放式槽结构,模拟了后齿蛇的带槽毒牙:类似于蛇牙,微针可以在毛细作用下,仅用轻轻的拇指压力,在几秒钟内快速有效地输送各种不同的液态药物和疫苗,而无需复杂的泵送系统。流体动力学模拟表明,受蛇牙启发的开放式槽结构能够快速地以毛细作用力输送具有不同表面张力和粘度的液体配方。我们证明,使用受蛇牙启发的微针贴片给药卵清蛋白和流感病毒,能够在豚鼠和小鼠中诱导出强烈的抗体产生和保护性免疫反应。