The Danish National Research Foundation and, Villum Foundation's Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Denmark and National Centre for Nano Fabrication and Characterization, DTU Nanolab, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
The Danish National Research Foundation and, Villum Foundation's Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Denmark and Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
Lab Chip. 2019 Sep 7;19(17):2905-2914. doi: 10.1039/c9lc00527g. Epub 2019 Aug 1.
Microfabrication techniques have been applied to develop micron-scale devices for oral drug delivery with a high degree of control over size, shape and material composition. Recently, microcontainers have been introduced as a novel approach to obtain unidirectional release to avoid luminal drug loss, enhance drug permeation, protect drug payload from the harsh environment of the stomach, and explore the ability for targeted drug delivery. However, in order to eventually pave the way for real life applications of these microfabricated drug delivery systems, it is necessary to fabricate them in biodegradable materials approved for similar applications and with strategies that potentially allow for large scale production. In this study, we for the first time evaluate biodegradable microcontainers for oral drug delivery. Asymmetric poly-ε-caprolactone (PCL) microcontainers with a diameter of 300 μm and a volume of 2.7 nL are fabricated with a novel single-step fabrication process. The microcontainers are loaded with the model drug paracetamol and coated with an enteric pH-sensitive Eudragit® S100 coating to protect the drug until it reaches the desired location in the small intestine. In vitro dissolution studies are performed to assess the drug load and release profile of the PCL microcontainers. Finally, in vivo studies in rats showed a higher bioavailability compared to conventional dosage forms and confirm the potential of biodegradable microcontainers for oral drug delivery.
微制造技术已被应用于开发用于口服药物输送的微米级装置，可高度控制尺寸、形状和材料组成。最近，微容器作为一种新方法被引入，以获得单向释放，避免腔道药物损失、增强药物渗透、保护药物有效负载免受胃部恶劣环境的影响，并探索靶向药物输送的能力。然而，为了最终为这些微制造药物输送系统的实际应用铺平道路，有必要使用可生物降解的材料来制造它们，这些材料已被批准用于类似的应用，并且具有可能允许大规模生产的策略。在这项研究中，我们首次评估了用于口服药物输送的可生物降解微容器。采用新颖的单步制造工艺制造了直径为 300μm、体积为 2.7nL 的不对称聚己内酯（PCL）微容器。微容器中装载有模型药物扑热息痛，并涂有肠溶 pH 敏感型 Eudragit® S100 涂层，以保护药物，直到它到达小肠的预期位置。进行体外溶解研究以评估 PCL 微容器的药物负载和释放特性。最后，大鼠体内研究表明与传统剂型相比具有更高的生物利用度，并证实了可生物降解微容器用于口服药物输送的潜力。
