Vaut Lukas, Juszczyk Julia J, Kamguyan Khorshid, Jensen Kristian E, Tosello Guido, Boisen Anja
The Danish National Research Foundation and Villum Foundation's Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
Department of Mechanical Engineering, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2478-2486. doi: 10.1021/acsbiomaterials.9b01760. Epub 2020 Mar 4.
So far, microdevices for oral drug delivery have been fabricated as square or cylindrical reservoir structures with a localized and unidirectional release. The fabrication is usually carried out using sophisticated and costly microfabrication techniques. Here, 3D printing of microreservoirs on sacrificial substrates is presented. This approach allows the devices to be accurately arranged in predetermined patterns, enabling implementation into batch production schemes in which the fabrication of the devices is linked to processing steps such as automated drug loading and sealing. Moreover, design and 3D printing of alternative geometries of minireservoirs featuring anchor-like surface structures for improved mucoadhesion and intestinal retention is demonstrated. Surface texturing of minireservoirs increases mucoadhesion of the devices up to two-fold compared to a nonstructured control. The structuring also leads to a strong bias in mucoadhesion in different orientations, which can facilitate a correct orientation of the devices and thus lead to unidirectional release of drugs toward the intestinal mucosa for increased drug uptake.
到目前为止，用于口服给药的微型装置已被制造成具有局部单向释放功能的方形或圆柱形储库结构。其制造通常采用复杂且昂贵的微制造技术。在此，介绍了在牺牲性基底上3D打印微储库的方法。这种方法允许将装置精确地排列成预定图案，从而能够应用于批量生产方案，其中装置的制造与诸如自动药物装载和密封等加工步骤相关联。此外，还展示了具有锚状表面结构的微型储库替代几何形状的设计和3D打印，以改善粘膜粘附和肠道滞留。与无结构对照相比，微型储库的表面纹理化使装置的粘膜粘附力提高了两倍。这种结构化还导致不同方向上粘膜粘附存在强烈偏差，这有助于装置的正确定向，从而实现药物向肠粘膜的单向释放，以增加药物吸收。
