Department of Biotechnology, Building 123, Yonsei University, 50 Yonsei-ro, Seoul, 03722, Seodaemun-gu, Korea.
Juvic Inc., Building 102, Yonsei Engineering Research Park, 50 Yonsei-ro, Seoul, 03722, Seodaemun-gu, Korea.
Sci Rep. 2018 Jan 18;8(1):1170. doi: 10.1038/s41598-018-19789-x.
Dissolving microneedles (DMNs) are microscopic needles capable of delivering encapsulated compounds and releasing them into the skin in a minimally invasive manner. Most studies indicate that encapsulating therapeutics in DMNs is an efficacious approach; however, the importance of evaluating the activity of encapsulated compounds, during the fabrication process, has not been examined in detail. Conducting an analysis of thermal, chemical, and physical stress factors, including temperature, pH, and the interaction of the polymer and therapeutics mixture during preparation, is essential for retaining the activity of encapsulated therapeutics during and after fabrication. Here, we optimised the thermal, chemical, and physical parameters for the fabrication of exendin-4 (Ex-4)-encapsulated DMNs (Ex-4 DMNs). Ex-4, a peptide agonist of glucagon-like peptide (GLP) receptor, is used for glycaemic control in patients with type 2 diabetes. Our findings indicate that optimising the parameters involved in DMN fabrication retained the activity of Ex-4 by up to 98.3 ± 1.5%. Ex-4 DMNs reduced the blood-glucose level in diabetic mice with efficiency similar to that of a subcutaneous injection. We believe that this study paves way for the commercialisation of an efficient and minimally invasive treatment for patients with type 2 diabetes.
溶解微针（DMNs）是能够以微创方式将封装化合物递送至皮肤并将其释放的微型针。大多数研究表明，将治疗药物封装在 DMNs 中是一种有效的方法；然而，在制造过程中评估封装化合物活性的重要性尚未得到详细研究。对热、化学和物理应激因素进行分析，包括温度、pH 值以及聚合物和治疗药物混合物在制备过程中的相互作用，对于在制造过程中和制造后保持封装治疗药物的活性至关重要。在这里，我们优化了用于制备外泌素-4（Ex-4）封装 DMNs（Ex-4 DMNs）的热、化学和物理参数。Ex-4 是胰高血糖素样肽（GLP）受体的肽激动剂，用于 2 型糖尿病患者的血糖控制。我们的研究结果表明，通过优化 DMN 制造中涉及的参数，可以将 Ex-4 的活性保持在 98.3±1.5%。Ex-4 DMNs 降低了糖尿病小鼠的血糖水平，其效率与皮下注射相当。我们相信，这项研究为开发针对 2 型糖尿病患者的高效、微创治疗方法铺平了道路。
