Fiering J, Mescher M J, Leary Swan E E, Holmboe M E, Murphy B A, Chen Z, Peppi M, Sewell W F, McKenna M J, Kujawa S G, Borenstein J T
Charles Stark Draper Laboratory, Cambridge, MA, USA.
Biomed Microdevices. 2009 Jun;11(3):571-8. doi: 10.1007/s10544-008-9265-5.
The development and optimization of many new drug therapies requires long-term local delivery with controlled, but variable dosage. Current methods for chronic drug delivery have limited utility because they either cannot deliver drugs locally to a specific organ or tissue, do not permit changes in delivery rate in situ, or cannot be used in clinical trials in an untethered, wearable configuration. Here, we describe a small, self-contained system for liquid-phase drug delivery. This system enables studies lasting several months and infusion rates can be programmed and modified remotely. A commercial miniature pump is integrated with microfabricated components to generate ultralow flow rates and stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses delivered at any interval of 1 min or longer. A unique feature of the system is the ability to infuse and immediately withdraw liquid, resulting in zero net volume transfer while compounds are exchanged by mixing and diffusion with endogenous fluid. We present in vitro results demonstrating repeatability of the delivered pulse volume for nearly 3 months. Furthermore, we present in vivo results in an otology application, infusing into the cochlea of a guinea pig a glutamate receptor antagonist, which causes localized and reversible changes in auditory sensitivity.
许多新型药物疗法的研发与优化需要长期局部给药，剂量可控但可变。目前的慢性药物递送方法效用有限，因为它们要么无法将药物局部递送至特定器官或组织，要么不允许原位改变递送速率，要么无法以无束缚、可穿戴的配置用于临床试验。在此，我们描述了一种用于液相药物递送的小型独立系统。该系统能够进行持续数月的研究，输注速率可远程编程和修改。一个商用微型泵与微制造部件集成在一起，以产生超低流速和冲程容积。溶液以小至370纳升的脉冲形式递送，脉冲可在1分钟或更长的任何间隔时间递送。该系统的一个独特功能是能够输注并立即抽出液体，从而在化合物通过与内源性液体混合和扩散进行交换时实现净体积转移为零。我们展示了体外结果，证明了近3个月内递送脉冲体积的可重复性。此外，我们展示了在耳科学应用中的体内结果，将一种谷氨酸受体拮抗剂注入豚鼠的耳蜗，这会引起听觉敏感性的局部和可逆变化。
