Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino, PU, Italy.
R&D Department, Idrofoglia s.r.l., Via Provinciale, 14, 61026 Lunano, PU, Italy.
Int J Pharm. 2021 Apr 15;599:120464. doi: 10.1016/j.ijpharm.2021.120464. Epub 2021 Mar 10.
During the last decade, an innovative lab on a chip technology known as microfluidics became popular in the pharmaceutical field to produce nanomedicines in a scalable way. Nevertheless, the predominant barriers for new microfluidics users are access to expensive equipment and device fabrication expertise. 3D printing technology promises to be an enabling new field that helps to overcome these drawbacks expanding the realm of microfluidics. Among 3D printing techniques, fused deposition modeling allows the production of devices with relatively inexpensive materials and printers. In this work, we developed two different microfluidic chips designed to obtain a passive micromixing by a "zigzag" bas-relief and by the presence of "split and recombine" channels. Computational fluid dynamics studies improved the evaluation of the mixing potential. A fused deposition modeling 3D printer was used to print the developed devices with polypropylene as manufacturing material. Then, two different model nanocarriers (i.e., polymeric nanoparticles and liposomes), loading cannabidiol as model drug, were formulated evaluating the influence of manufacturing parameters on the final nanocarrier characteristics with a design of experiments approach (2-level full factorial design). Both the chips showed an effective production of nanocarriers with tunable characteristics and with an efficient drug loading. These polypropylene-based microfluidic chips could represent an affordable and low-cost alternative to common microfluidic devices for the effective manufacturing of nanomedicines (both polymer- and lipid-based) after appropriate tuning of manufacturing parameters.
在过去的十年中,一种称为微流控的创新芯片技术在制药领域变得流行起来,能够以可扩展的方式生产纳米药物。然而,新的微流控用户面临的主要障碍是昂贵的设备和器件制造专业知识。3D 打印技术有望成为一个新的领域,帮助克服这些缺点,扩大微流控的应用范围。在 3D 打印技术中,熔融沉积建模允许使用相对廉价的材料和打印机生产设备。在这项工作中,我们开发了两种不同的微流控芯片,旨在通过“之字形”浅浮雕和“分裂和重组”通道获得被动微混合。计算流体动力学研究提高了混合潜力的评估。使用熔融沉积建模 3D 打印机,以聚丙烯为制造材料打印开发的器件。然后,使用两种不同的模型纳米载体(即聚合物纳米颗粒和脂质体),负载作为模型药物的大麻二酚,通过实验设计方法(2 水平完全析因设计)评估制造参数对最终纳米载体特性的影响。两种芯片都显示出有效生产具有可调特性的纳米载体,并具有高效的药物负载。这些基于聚丙烯的微流控芯片可以作为一种经济实惠的替代方案,用于通用微流控设备,用于制造有效的纳米药物(基于聚合物和脂质的纳米药物),在适当调整制造参数后。