Soto Robert J, Schofield Jonathon B, Walter Shaylyn E, Malone-Povolny Maggie J, Schoenfisch Mark H
Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
ACS Sens. 2017 Jan 27;2(1):140-150. doi: 10.1021/acssensors.6b00623. Epub 2016 Dec 15.
Nitric oxide (NO)-releasing polymers have proven useful for improving the biocompatibility of in vivo glucose biosensors. Unfortunately, leaching of the NO donor from the polymer matrix remains a critical design flaw of NO-releasing membranes. Herein, a toolbox of NO-releasing silica nanoparticles (SNPs) was utilized to systematically evaluate SNP leaching from a diverse selection of biomedical-grade polyurethane sensor membranes. Glucose sensor analytical performance and NO-release kinetics from the sensor membranes were also evaluated as a function of particle and polyurethane (PU) chemistries. Particles modified with N-diazeniumdiolate NO donors were prone to leaching from PU membranes due to the zwitterionic nature of the NO donor modification. Leaching was minimized (<5% of the entrapped silica over 1 month) in low water uptake PUs. However, SNP modification with neutral S-nitrosothiol (RSNO) NO donors lead to biphasic leaching behavior. Particles with low alkanethiol content (<3.0 wt % sulfur) leached excessively from a hydrogel PU formulation (HP-93A-100 PU), while particles with greater degrees of thiol modification did not leach from any of the PUs tested. A functional glucose sensor was developed using an optimized HP-93A-100 PU membrane doped with RSNO-modified SNPs as the outer, glucose diffusion-limiting layer. The realized sensor design responded linearly to physiological concentrations of glucose (minimum 1-21 mM) over 2 weeks incubation in PBS and released NO at >0.8 pmol cm s for up to 6 days with no detectable (<0.6%) particle leaching.
已证明释放一氧化氮（NO）的聚合物有助于改善体内葡萄糖生物传感器的生物相容性。不幸的是，NO供体从聚合物基质中的浸出仍然是释放NO的膜的一个关键设计缺陷。在此，利用一个释放NO的二氧化硅纳米颗粒（SNP）工具箱，系统地评估了从各种生物医学级聚氨酯传感器膜中浸出的SNP。还评估了传感器膜的葡萄糖传感器分析性能和NO释放动力学，作为颗粒和聚氨酯（PU）化学性质的函数。由于NO供体修饰的两性离子性质，用二醇二氮烯鎓NO供体修饰的颗粒易于从PU膜中浸出。在低吸水率的PU中，浸出最小化（超过1个月，截留二氧化硅的<5%）。然而，用中性S-亚硝基硫醇（RSNO）NO供体进行的SNP修饰导致了双相浸出行为。低链烷硫醇含量（<3.0 wt%硫）的颗粒从水凝胶PU配方（HP-93A-100 PU）中过度浸出，而硫醇修饰程度更高的颗粒在任何测试的PU中均未浸出。使用掺杂有RSNO修饰的SNP的优化HP-93A-100 PU膜作为外部葡萄糖扩散限制层，开发了一种功能性葡萄糖传感器。在PBS中孵育2周期间，实现的传感器设计对生理浓度的葡萄糖（最低1-21 mM）呈线性响应，并且在长达6天的时间内以>0.8 pmol cm s的速率释放NO，且未检测到（<0.6%）颗粒浸出。
