College of Pharmacy, University of Texas at Austin , Austin, TX, USA.
Drug Deliv Transl Res. 2018 Dec;8(6):1828-1843. doi: 10.1007/s13346-017-0466-4.
Recently, results have been published for the first successful phase I human clinical trial investigating the use of dissolving polymeric microneedles… Even so, further clinical development represents an important hurdle that remains in the translation of microneedle technology to approved products. Specifically, the potential for accumulation of polymer within the skin upon repeated application of dissolving and coated microneedles, combined with a lack of safety data in humans, predicates a need for further clinical investigation. Polymers are an important consideration for microneedle technology-from both manufacturing and drug delivery perspectives. The use of polymers enables a tunable delivery strategy, but the scalability of conventional manufacturing techniques could arguably benefit from further optimization. Micromolding has been suggested in the literature as a commercially viable means to mass production of both dissolving and swellable microneedles. However, the reliance on master molds, which are commonly manufactured using resource intensive microelectronics industry-derived processes, imparts notable material and design limitations. Further, the inherently multi-step filling and handling processes associated with micromolding are typically batch processes, which can be challenging to scale up. Similarly, conventional microneedle coating processes often follow step-wise batch processing. Recent developments in microneedle coating and manufacturing techniques are highlighted, including micromilling, atomized spraying, inkjet printing, drawing lithography, droplet-born air blowing, electro-drawing, continuous liquid interface production, 3D printing, and polyelectrolyte multilayer coating. This review provides an analysis of papers reporting on potentially scalable production techniques for the coating and manufacturing of microneedles.
最近，首次成功进行的 I 期人体临床试验结果公布，该试验调查了可溶解聚合物微针的使用……即便如此，进一步的临床开发仍然代表着将微针技术转化为已批准产品的重要障碍。具体而言，在可溶解和涂层微针的重复应用中，聚合物在皮肤内的累积的可能性，加上缺乏人体安全性数据，预示着需要进一步的临床研究。聚合物是微针技术的一个重要考虑因素——无论是从制造还是药物输送的角度来看。聚合物的使用能够实现可调节的输送策略，但传统制造技术的可扩展性可能需要进一步优化。微成型已在文献中被提出，作为可溶解和可膨胀微针大规模生产的一种商业可行手段。然而，对母模的依赖，这些母模通常使用资源密集型微电子行业衍生的工艺制造，赋予了显著的材料和设计限制。此外，与微成型相关的固有多步填充和处理过程通常是批处理过程，这可能难以扩大规模。同样，传统的微针涂层工艺通常遵循分步批处理。本文重点介绍了微针涂层和制造技术的最新进展，包括微铣削、雾化喷涂、喷墨打印、绘图光刻、液滴空气吹塑、电拉伸、连续液界面生产、3D 打印和聚电解质多层涂层。本文对报道微针涂层和制造的潜在可扩展生产技术的论文进行了分析。
