Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 2300, Einsteinweg 55, 2333 CC Leiden, the Netherlands.
Tumor Immunology Group, Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; TECO Development GmbH, 53359 Rheinbach, Germany.
Int J Pharm. 2021 May 1;600:120473. doi: 10.1016/j.ijpharm.2021.120473. Epub 2021 Mar 16.
Dissolving microneedle arrays (dMNAs) are promising devices for intradermal vaccine delivery. The aim of this study was to develop a reproducible fabrication method for dMNAs based on an automated nano-droplet dispensing system that minimizes antigen waste. First, a polymer formulation was selected to dispense sufficiently small droplets (<18 nL) that can enter the microneedle cavities (base diameter 330 µm). Besides, three linear stages were assembled to align the dispenser with the cavities, and a vacuum chamber was designed to fill the cavities with dispensed droplets without entrapped air. Lastly, the dispenser and stages were incorporated to build a fully automated system. To examine the function of dMNAs as a vaccine carrier, ovalbumin was loaded in dMNAs by dispensing a mixture of ovalbumin and polymer formulation, followed by determining the ovalbumin loading and release into the skin. The results demonstrate that functional dMNAs which can deliver antigen into the skin were successfully fabricated via the automatic fabrication system, and hardly any antigen waste was encountered. Compared to the method that centrifuges the mould, it resulted in a 98.5% volume reduction of antigen/polymer solution and a day shorter production time. This system has potential for scale-up of manufacturing to an industrial scale.
溶解微针阵列（dMNAs）是一种很有前途的皮内疫苗递送装置。本研究的目的是开发一种基于自动化纳升级液滴分配系统的可重复制造方法，以最大限度地减少抗原浪费。首先，选择了一种聚合物配方来分配足够小的液滴（<18 nL），这些液滴可以进入微针腔（基底直径 330 µm）。此外，组装了三个线性工作台来将分配器与腔室对准，并设计了一个真空室来用分配的液滴填充腔室而不会夹带空气。最后，将分配器和工作台集成在一起，构建了一个全自动系统。为了检验 dMNAs 作为疫苗载体的功能，通过分配卵清蛋白和聚合物配方的混合物将卵清蛋白加载到 dMNAs 中，然后测定卵清蛋白在皮肤中的加载和释放。结果表明，通过自动制造系统成功制造了可将抗原递送入皮肤的功能性 dMNAs，并且几乎没有遇到任何抗原浪费。与离心模具的方法相比，它将抗原/聚合物溶液的体积减少了 98.5%，并将生产时间缩短了一天。该系统具有在工业规模上扩大制造规模的潜力。
