MyLife Technologies B.V., Leiden Bio Science Park, BioPartner 4, Robert Boyleweg 4, Unit 4358, 2333 CG Leiden, the Netherlands.
MyLife Technologies B.V., Leiden Bio Science Park, BioPartner 4, Robert Boyleweg 4, Unit 4358, 2333 CG Leiden, the Netherlands.
Eur J Pharm Sci. 2020 Jul 1;150:105331. doi: 10.1016/j.ejps.2020.105331. Epub 2020 May 26.
Conventional transdermal drug patches have been on the market since 1997 but their applicability for drug delivery is limited: currently only nearly two dozen of molecules have been approved by the regulatory authorities for transdermal administration and have reached the market. The possibilities for drug delivery via the skin can be improved and expanded by using microneedle patch technologies. However, most microneedle patches focus on the delivery of low amounts of drugs that are generally very potent due to the small dimensions of the microneedle systems. In this study nanoporous microneedle arrays (npMNAs) were combined with a liquid drug reservoir. The parameters that influence the diffusion of memantine from the drug reservoir through the npMNAs in an acceptor solution were investigated. Based on these results a model was developed to predict the diffusion of low-molecular-weight drugs as a function of npMNA properties (i.e., backplate thickness and surface area) and reservoir properties (i.e., volume and drug concentration). This generated an in silico model to predict the release of low-molecular-weight drug from a drug reservoir through a microneedle array into receptor solution, showed a good correlation with the delivery of memantine in a preclinical minipig study. The drug release rates by the npMNAs can be tuned and allow for both zero and first order release kinetics. Summarizing, this work shows that the npMNA technology is a versatile drug delivery system. The npMNAs can be combined with a (seamlessly connected) external drug reservoir and this integrated drug delivery system can be used to deliver at least 9 mg of memantine over 72 h in a preclinical minipig study.
传统的透皮药物贴片自 1997 年以来就已经上市，但它们的药物输送适用性有限：目前仅有约二十几种分子经监管机构批准用于透皮给药并已进入市场。通过使用微针贴片技术，可以提高和扩展药物经皮输送的可能性。然而，大多数微针贴片都专注于输送少量的药物，这些药物由于微针系统的小尺寸通常非常有效。在这项研究中，纳米多孔微针阵列（npMNAs）与液体药物储库相结合。研究了影响药物从药物储库通过 npMNAs 扩散到接受溶液中的因素。基于这些结果，开发了一个模型来预测低分子量药物的扩散作为 npMNA 特性（即背板厚度和表面积）和储库特性（即体积和药物浓度）的函数。这生成了一个用于预测低分子量药物从药物储库通过微针阵列释放到受体溶液中的计算机模型，与临床前小型猪研究中释放盐酸美金刚的情况具有很好的相关性。npMNAs 的药物释放率可以进行调整，并允许零级和一级释放动力学。总之，这项工作表明 npMNA 技术是一种多功能的药物输送系统。npMNAs 可以与（无缝连接的）外部药物储库结合，这种集成的药物输送系统可以在临床前小型猪研究中至少输送 9 毫克盐酸美金刚，持续 72 小时。
