A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery
A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery
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DOI：
10.1039/c0lc00013b
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发表时间：
2010-01-01
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
这份手稿展示了一种机械坚固的可植入纳米流体膜，能够在与临床应用相关的范围内可调长期零级释放治疗剂。膜，与纳米通道小至5 nm，允许独立控制剂量和机械强度，通过集成的高密度短纳米通道平行于膜表面与垂直的微通道和宏通道与周围的解决方案接口。这些纳米流体膜是使用精密硅制造技术在绝缘体上硅衬底上创建的，从而能够精确控制单分散纳米通道的尺寸和表面粗糙度。分析物的零级释放是通过利用分子与表面的相互作用来实现的，当流体被限制在纳米级时，分子与表面的相互作用主导扩散传输。在这项研究中，我们研究了纳米流体膜的性能，使用定制的扩散和气体测试装置，以量化分子释放速率和工艺均匀性以及机械强度，使用基于气体的爆裂测试。约束的零级释放的动力学探测与分子呈现一系列的大小，电荷状态，和结构构象。最后，确定分子流体动力学直径与纳米通道尺寸的最佳比率，以确保每个测试分子的零级释放。
This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro-and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness. Zero-order release of analytes is achieved by exploiting molecule to surface interactions which dominate diffusive transport when fluids are confined to the nanoscale. In this study we investigate the nanofluidic membrane performance using custom diffusion and gas testing apparatuses to quantify molecular release rate and process uniformity as well as mechanical strength using a gas based burst test. The kinetics of the constrained zero-order release is probed with molecules presenting a range of sizes, charge states, and structural conformations. Finally, an optimal ratio of the molecular hydrodynamic diameter to the nanochannel dimension is determined to assure zero-order release for each tested molecule.