Forouzandeh Farzad, Ahamed Nuzhet N, Zhu Xiaoxia, Bazard Parveen, Goyal Krittika, Walton Joseph P, Frisina Robert D, Borkholder David A
Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623, USA.
Department of Medical Engineering, Global Center for Hearing & Speech Research, University of South Florida, Tampa, FL 33620, USA.
Pharmaceuticals (Basel). 2021 Jun 4;14(6):538. doi: 10.3390/ph14060538.
Here we present a 3D-printed, wirelessly controlled microsystem for drug delivery, comprising a refillable microreservoir and a phase-change peristaltic micropump. The micropump structure was inkjet-printed on the back of a printed circuit board around a catheter microtubing. The enclosure of the microsystem was fabricated using stereolithography 3D printing, with an embedded microreservoir structure and integrated micropump. In one configuration, the microsystem was optimized for murine inner ear drug delivery with an overall size of 19 × 13 × 3 mm. Benchtop results confirmed the performance of the device for reliable drug delivery. The suitability of the device for long-term subcutaneous implantation was confirmed with favorable results of implantation of a microsystem in a mouse for six months. The drug delivery was evaluated in vivo by implanting four different microsystems in four mice, while the outlet microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion, demonstrating similar results with syringe pump infusion. Although demonstrated for one application, this low-cost design and fabrication methodology is scalable for use in larger animals and humans for different clinical applications/delivery sites.
在此，我们展示了一种用于药物递送的3D打印无线控制微系统，它由一个可再填充的微储液器和一个相变蠕动微泵组成。微泵结构通过喷墨打印在围绕导管微管的印刷电路板背面。微系统的外壳采用立体光刻3D打印制造，具有嵌入式微储液器结构和集成微泵。在一种配置中，该微系统针对小鼠内耳药物递送进行了优化，总体尺寸为19×13×3毫米。台式实验结果证实了该装置进行可靠药物递送的性能。通过将一个微系统在小鼠体内植入六个月的良好结果，证实了该装置适用于长期皮下植入。通过在四只小鼠体内植入四个不同的微系统来评估体内药物递送情况，同时将出口微管植入圆窗膜龛，以50纳升/分钟的速度注入一种已知的耳毒性化合物（水杨酸钠），持续20分钟。在输注过程中测量畸变产物耳声发射阈值和幅度的实时变化，结果表明与注射泵输注相似。尽管仅针对一种应用进行了展示，但这种低成本的设计和制造方法可扩展用于更大的动物和人类的不同临床应用/递送部位。
