Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China; Key Laboratory of Biomedical Materials of Natural Macromolecules, Beijing University of Chemical Technology, Ministry of Education, Beijing 100029, PR China.
Department of Dermatology, China-Japan Friendship Hospital, East Street Cherry Park, Chaoyang District, Beijing 100029, PR China; Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, PR China.
Eur J Pharm Biopharm. 2021 Mar;160:1-8. doi: 10.1016/j.ejpb.2021.01.005. Epub 2021 Jan 20.
Dissolving microneedles (DMNs) are widely used in drug delivery systems since they are based on one-step application, which is simple and convenient for patients, especially for the patients such as diabetes who need daily or long-term self-administration. In general, the matrix materials of DMNs are water-soluble materials that can release the encapsulated drugs gradually by dissolving in the skin without generating sharp needle waste. However, the matrix materials of DMNs will also leave in the skin after application. Thus, it is vital to evaluate whether the matrix material of DMNs dissolved in the skin will cause health risks such as toxicity to the body or some skin-related complications to patients who frequent or long-term administration. In this work, PVA, as one of the typical matrix materials of DMNs, was selected to prepare the DMNs to research the safety of PVA-based MNs to the body after being dissolved in the skin. Briefly, in a 160 - days trial, the healthy mice were daily administrated by PVA MNs. The results showed that PVA materials mainly accumulated in the skin tissues of mice after dissolving and the concentration of PVA in the insertion sites gradually decreased and was almost undetectable at 6 days after administration. The observation of general conditions, blood hematological analysis and histological examinations of the mice demonstrated that the PVA-based MNs do not cause appreciable toxicity to the healthy mice after daily insertion in a 160 - days trial. Altogether, these results encourage further studies of PVA MNs for biomedical applications and support translation of PVA-based DMNs from pre-clinical development into clinical trials.
可溶解微针 (DMNs) 广泛应用于药物传递系统，因为它们基于一步应用，对患者来说简单方便，尤其适用于需要每日或长期自我给药的糖尿病患者等。一般来说，DMNs 的基质材料是水溶性材料，可在皮肤中逐渐溶解释放包裹的药物，而不会产生尖锐的针废物。然而，DMNs 的基质材料在应用后也会留在皮肤中。因此，评估 DMNs 溶解在皮肤中的基质材料是否会对频繁或长期给药的患者的身体造成毒性等健康风险或一些与皮肤相关的并发症至关重要。在这项工作中，PVA 作为 DMNs 的典型基质材料之一，被选来制备 DMNs，以研究 PVA 基 MNs 溶解在皮肤后对身体的安全性。简而言之，在 160 天的试验中，健康小鼠每天接受 PVA MN 给药。结果表明，PVA 材料在溶解后主要积聚在小鼠的皮肤组织中，并且在给药后 6 天，插入部位的 PVA 浓度逐渐降低，几乎无法检测到。对小鼠的一般情况、血液血液学分析和组织学检查表明，在 160 天的试验中，每日插入 PVA 基 MNs 不会对健康小鼠造成明显毒性。总之，这些结果鼓励进一步研究 PVA MNs 在生物医学中的应用，并支持将基于 PVA 的 DMNs 从临床前开发转化为临床试验。
