Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , China.
ACS Appl Mater Interfaces. 2018 Oct 10;10(40):33986-33992. doi: 10.1021/acsami.8b12200. Epub 2018 Sep 26.
We report in this work the fabrication of a flow-through silica nanochannel membrane (SNM) for controlled drug release applications. The ultrathin SNM consists of parallel nanochannels with a uniform diameter of ∼2.3 nm and a density of 4 × 10 cm, which provide simultaneously high permeability and size selectivity toward small molecules. The track-etched porous polyethylene terephthalate film premodified with silane on its surface was used to support the ultrathin SNM via irreversible covalent bond formation, thus offering mechanical strength, flexibility, and stability to the ultrathin SNM for continuous and long-term use. Alkylamines were subsequently grafted onto the SNM surface to modulate the "on" and "off" state of nanochannels by medium pH for controlled drug release. Thiamphenicol glycinate hydrochloride (TPG), an intestinal drug, was studied as a model to permeate through an ultrathin SNM in both simulated gastric fluid (pH = 1.2) and simulated intestinal fluid (pH = 7.5). The release in the latter case was 178 times faster than that in the former. Moreover, a nearly zero-order constant release of TPG via single-file diffusion was achieved up to 24 h, demonstrating the feasibility of sustained and continuous release of small-molecule drugs in a pH-controlled manner.
我们在这项工作中报告了一种用于控制药物释放应用的流通式硅纳米通道膜 (SNM) 的制造。这种超薄 SNM 由具有均匀直径约 2.3nm 和 4×10cm 密度的平行纳米通道组成，为小分子提供了同时具有高渗透性和尺寸选择性。经过表面硅烷预处理的聚对苯二甲酸乙二醇酯膜通过不可逆的共价键形成来支撑超薄 SNM，从而为超薄 SNM 提供机械强度、灵活性和稳定性，以实现连续和长期使用。随后，烷基胺被接枝到 SNM 表面，通过介质 pH 值来调节纳米通道的“开”和“关”状态，以实现控制药物释放。作为模型药物，我们研究了盐酸丁胺卡那霉素（TPG）在模拟胃液（pH = 1.2）和模拟肠液（pH = 7.5）中通过超薄 SNM 的渗透。在后一种情况下的释放速度比在前一种情况下快 178 倍。此外，通过单分子扩散实现了 TPG 的近零级恒速释放，长达 24 小时，证明了以 pH 值控制的方式实现小分子药物持续和连续释放的可行性。
