Kara Aytug, Vassiliadou Athina, Ongoren Baris, Keeble William, Hing Richard, Lalatsa Aikaterini, Serrano Dolores R
Pharmaceutics and Food Technology Department, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Biomaterials, Bio-engineering and Nanomedicine (BioN) Lab, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, UK.
Pharmaceutics. 2021 Dec 10;13(12):2134. doi: 10.3390/pharmaceutics13122134.
Currently, there is an unmet need to manufacture nanomedicines in a continuous and controlled manner. Three-dimensional (3D) printed microfluidic chips are an alternative to conventional PDMS chips as they can be easily designed and manufactured to allow for customized designs that are able to reproducibly manufacture nanomedicines at an affordable cost. The manufacturing of microfluidic chips using existing 3D printing technologies remains very challenging because of the intricate geometry of the channels. Here, we demonstrate the manufacture and characterization of nifedipine (NFD) polymeric nanoparticles based on Eudragit L-100 using 3D printed microfluidic chips with 1 mm diameter channels produced with two 3D printing techniques that are widely available, stereolithography (SLA) and fuse deposition modeling (FDM). Fabricated polymeric nanoparticles showed good encapsulation efficiencies and particle sizes in the range of 50-100 nm. SLA chips possessed better channel resolution and smoother channel surfaces, leading to smaller particle sizes similar to those obtained by conventional manufacturing methods based on solvent evaporation, while SLA manufactured nanoparticles showed a minimal burst effect in acid media compared to nanoparticles fabricated with FDM chips. Three-dimensional printed microfluidic chips are a novel and easily amenable cost-effective strategy to allow for customization of the design process for continuous manufacture of nanomedicines under controlled conditions, enabling easy scale-up and reducing nanomedicine development times, while maintaining high-quality standards.
目前，以连续且可控的方式制造纳米药物仍存在未满足的需求。三维（3D）打印微流控芯片是传统聚二甲基硅氧烷（PDMS）芯片的一种替代方案，因为它们可以轻松设计和制造，以实现定制设计，能够以可承受的成本可重复地制造纳米药物。由于通道的复杂几何形状，使用现有的3D打印技术制造微流控芯片仍然非常具有挑战性。在此，我们展示了基于Eudragit L - 100的硝苯地平（NFD）聚合物纳米颗粒的制造和表征，该纳米颗粒使用具有1毫米直径通道的3D打印微流控芯片制造，这些芯片由两种广泛可用的3D打印技术制造而成，即立体光刻（SLA）和熔融沉积建模（FDM）。制备的聚合物纳米颗粒显示出良好的包封效率，粒径在50 - 100纳米范围内。SLA芯片具有更好的通道分辨率和更光滑的通道表面，导致粒径更小，类似于通过基于溶剂蒸发的传统制造方法获得的粒径，而与用FDM芯片制造的纳米颗粒相比，SLA制造的纳米颗粒在酸性介质中显示出最小的突释效应。三维打印微流控芯片是一种新颖且易于采用的具有成本效益的策略，可实现设计过程的定制，以便在受控条件下连续制造纳米药物，实现易于放大并缩短纳米药物的开发时间，同时保持高质量标准。
