Amoyav Benzion, Goldstein Yoel, Steinberg Eliana, Benny Ofra
The Institute for Drug Research, School of Pharmacy, The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Pharmaceutics. 2020 Dec 23;13(1):13. doi: 10.3390/pharmaceutics13010013.
Microfluidics research for various applications, including drug delivery, cell-based assays and biomedical research has grown exponentially. Despite this technology's enormous potential, drawbacks include the need for multistep fabrication, typically with lithography. We present a one-step fabrication process of a microfluidic chip for drug dissolution assays based on a 3D printing technology. Doxorubicin porous and non-porous microspheres, with a mean diameter of 250µm, were fabricated using a conventional "batch" or microfluidic method, based on an optimized solid-in-oil-in-water protocol. Microspheres fabricated with microfluidics system exhibited higher encapsulation efficiency and drug content as compared with batch formulations. We determined drug release profiles of microspheres in varying pH conditions using two distinct dissolution devices that differed in their mechanical barrier structures. The release profile of the "V" shape barrier was similar to that of the dialysis sac test and differed from the "basket" barrier design. Importantly, a cytotoxicity test confirmed biocompatibility of the printed resin. Finally, the chip exhibited high durability and stability, enabling multiple recycling sessions. We show how the combination of microfluidics and 3D printing can reduce costs and time, providing an efficient platform for particle production while offering a feasible cost-effective alternative to clean-room facility polydimethylsiloxane-based chip microfabrication.
用于包括药物递送、基于细胞的分析和生物医学研究等各种应用的微流控研究呈指数级增长。尽管这项技术具有巨大潜力，但其缺点包括通常需要光刻等多步制造工艺。我们展示了一种基于3D打印技术的用于药物溶解分析的微流控芯片的一步制造工艺。使用基于优化的水包油包固方案的传统“批量”或微流控方法，制备了平均直径为250μm的阿霉素多孔和无孔微球。与批量制剂相比，用微流控系统制备的微球表现出更高的包封效率和药物含量。我们使用两种机械屏障结构不同的独特溶解装置，测定了微球在不同pH条件下的药物释放曲线。“V”形屏障的释放曲线与透析袋试验相似，与“篮式”屏障设计不同。重要的是，细胞毒性试验证实了打印树脂的生物相容性。最后，该芯片表现出高耐久性和稳定性，能够进行多次循环使用。我们展示了微流控和3D打印的结合如何能够降低成本和时间，为颗粒生产提供一个高效平台，同时为洁净室设施基于聚二甲基硅氧烷的芯片微制造提供一种可行的经济高效替代方案。
