A low-voltage electrokinetic nanochannel drug delivery system
A low-voltage electrokinetic nanochannel drug delivery system
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DOI：
10.1039/c1lc00001b
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发表时间：
2011-01-01
期刊：
影响因子：
6.1
通讯作者：
Liu, Xuewu
中科院分区：
文献类型：
--
作者：
Fine, Daniel;Grattoni, Alessandro;Liu, Xuewu
最近的工作已经阐明了重要的新的治疗范例的潜力，包括节拍递送和时间疗法，其中治疗施用的精确时间和位置对疗效和毒性具有显著影响。需要新的药物递送结构，不仅以精确的速率连续释放药物，而且使其释放与昼夜节律周期同步。我们提出了一种主动控制的纳米流体膜，利用电泳来控制药物释放的幅度，持续时间和时间。使用高精度硅制造技术生产的膜具有集成在入口和出口处的铂电极，其允许在低施加电压（等于或低于2VDC）下放大和逆转分析物递送。使用荧光光谱法、荧光显微镜和溶菌酶特异性生物测定法，用异硫氰酸荧光素结合牛血清白蛋白和溶菌酶的溶液证明了装置操作，并表征了长期分子释放和释放可逆性。通过理论和实验相结合的分析，电泳和电渗的相对贡献进行了研究。膜在2 VDC下的临床相关电泳释放速率超过被动释放近一个数量级，表明有可能实现治疗范例目标。
Recent work has elucidated the potential of important new therapeutic paradigms, including metronomic delivery and chronotherapy, in which the precise timing and location of therapeutic administration has a significant impact on efficacy and toxicity. New drug delivery architectures are needed to not only release drug continuously at precise rates, but also synchronize their release with circadian cycles. We present an actively controlled nanofluidic membrane that exploits electrophoresis to control the magnitude, duration, and timing of drug release. The membrane, produced using high precision silicon fabrication techniques, has platinum electrodes integrated at the inlet and outlet that allow both amplification and reversal of analyte delivery with low applied voltage (at or below 2 VDC). Device operation was demonstrated with solutions of both fluorescein isothiocyanate conjugated bovine serum albumin and lysozyme using fluorescence spectroscopy, fluorescence microscopy, and a lysozyme specific bio-assay and has been characterized for long-term molecular release and release reversibility. Through a combination of theoretical and experimental analysis, the relative contributions of electrophoresis and electroosmosis have been investigated. The membrane's clinically relevant electrophoretic release rate at 2 VDC exceeds the passive release by nearly one order of magnitude, demonstrating the potential to realize the therapeutic paradigm goal.