Bradshaw Taron M, Johnson Courtney R, Broberg Christopher A, Anderson Darci E, Schoenfisch Mark H
Department of Chemistry, University of North Carolina at Chapel Hill, North Carolina, 27599, United States.
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina, 27599, United States.
Sens Actuators B Chem. 2024 Apr 15;405. doi: 10.1016/j.snb.2024.135311. Epub 2024 Jan 10.
Nitric oxide (NO) release from -nitrosothiol-modified mesoporous silica nanoparticles imbedded in the diffusion limiting layer of a glucose sensor has been demonstrated as an effective strategy for mitigating the foreign body response common to sensor implantation, resulting in improved analytical performance. With respect to potential clinical translation of this approach, the effects of sterilization on NO-releasing biosensors require careful evaluation, as NO donor chemistry is sensitive to temperature and environment. Herein, we evaluated the influence of multiple sterilization methods on 1) sterilization success; 2) NO payload; and 3) sensor performance to establish the commercialization potential of NO-releasing glucose sensors. Sensors were treated with ethylene oxide gas, the most common sterilization method for intricate medical devices, which led to undesirable (i.e., premature) release of NO. To reduce NO loss, alternative sterilization methods that were studied included exposure to ultraviolet (UV) light and immersion in 70% ethanol (EtOH). Sterilization cycle times required to reach a 10 sterility assurance level were determined for both UV light and 70% EtOH against Gram-negative and -positive bacteria. The longest sterilization cycle times (258 s and 628 s for 70% EtOH and UV light, respectively) resulted in a negligible impact on benchtop sensor performance. However, sterilization with 70% ethanol resulted in a reduced NO-release duration. Ultraviolet light exposure for ~10 min proved successful at eliminating bacteria without compromising NO payloads or durations and presents as the most promising method for sterilization of these sensors. In addition, storage of NO-releasing sensor membranes at -20 and -80°C resulted in preservation of NO release for 6 and 12 months, respectively.
已证明，嵌入葡萄糖传感器扩散限制层的亚硝基硫醇修饰的介孔二氧化硅纳米颗粒释放一氧化氮（NO）是减轻传感器植入常见异物反应的有效策略，从而提高了分析性能。就该方法的潜在临床转化而言，由于NO供体化学对温度和环境敏感，因此灭菌对NO释放型生物传感器的影响需要仔细评估。在此，我们评估了多种灭菌方法对以下方面的影响：1）灭菌成功率；2）NO含量；3）传感器性能，以确定NO释放型葡萄糖传感器的商业化潜力。传感器用环氧乙烷气体处理，这是复杂医疗器械最常用的灭菌方法，但导致了NO的不良（即过早）释放。为减少NO损失，研究的替代灭菌方法包括紫外线（UV）照射和浸入70%乙醇（EtOH）中。针对革兰氏阴性菌和阳性菌，确定了达到10级无菌保证水平所需的UV光和70% EtOH的灭菌周期时间。最长的灭菌周期时间（70% EtOH和UV光分别为258秒和628秒）对台式传感器性能的影响可忽略不计。然而，用70%乙醇灭菌导致NO释放持续时间缩短。约10分钟的紫外线照射成功消除了细菌，同时不影响NO含量或持续时间，是这些传感器最有前景的灭菌方法。此外，将NO释放型传感器膜储存在-20°C和-80°C下，NO释放分别可保存6个月和12个月。
