Plasma clearance of water soluble and albumin bound toxins using graphene oxide nanoengineered laminates

使用氧化石墨烯纳米工程层压板清除水溶性和白蛋白结合毒素

• 批准号: 9387567
• 负责人: THOMAS R GABORSKI
• 金额: $ 23.23万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387567
• 关键词: Acute; Adhesions; Adsorption; Albumins; Animal Model; Anions; Area; Artificial Liver; Bilirubin; Blood; Blood Platelets; Blood Substitutes; Body Water; Carbon; Cells; Cellulose; Complement; Custom; Device Designs; Devices; Dialysis procedure; Drug Metabolic Detoxication; End stage renal failure; Excision; Goals; Hemodialysis; Hour; Human; Kidney Diseases; Kidney Failure; Laboratories; Liver Failure; Liver diseases; Liver support system; Measurement; Medical; Medicare; Membrane; Methods; Miniaturization; Modification; Monitor; Organ Transplantation; Organ failure; Oxides; Patients; Permeability; Plasma; Polymers; Property; Quality of life; Serum Albumin; Silicon; Surface; Surface Properties; System; Techniques; Technology; Testing; Thick; Thinness; Toxin; United States; Urea; Water; Weight; Work; analog; base; beta-2 Microglobulin; cytochrome c; flexibility; graphene; improved; lipophilicity; miniaturize; molecular sieving; nanoengineering; nanoscale; novel; prototype; scale up; success

Abstract Patients with end-stage kidney and liver disease as well as acute organ failure are unable to maintain the necessary clearance of toxins and require blood-purification techniques or organ transplant. Over 400,000 end-stage renal disease (ESRD) patients receive regular hemodialysis (HD) treatments in the United States. A smaller number receive artificial liver support therapy for detoxification and liver failure. These blood purification techniques place an extremely high financial burden on our medical system with sometimes questionable efficacy and relatively poor quality of life. ESRD treatment alone accounts for 7% of all Medicare spending ($31B). The membrane and adsorption technology behind these treatments has been slow to evolve over the last few decades, limiting the opportunity to make significant improvements. Graphene oxide (GO) has the potential to radically improve and change hemodialysis and liver support systems because GO bilayers are the thinnest possible molecular sieve and nanoscale-spaced GO stacks offer unparalleled adsorptive capacity. The scientific premise behind the use of GO nanoengineered laminates for the clearance of water-soluble and albumin- bound toxins is two-fold. First, prior work has demonstrated that the use of ultrathin nanoporous membranes enables the reduction of laboratory-scale dialyzers by two orders of magnitude compared to conventional polymeric membranes due to dramatically increased permeability, while maintaining size-selectivity. We hypothesize that GO nanoengineered laminate membranes will further reduce required membrane area by at least another order of magnitude based on thinness (<10nm) and increased permeability. Second, albumin-bound toxins have traditionally been removed using anion- exchange columns or porous matrices of activated carbon. Nanospaced GO laminates offer a theoretical limit on surface area within a fixed volume that is likely to exceed conventional adsorbent materials by orders of magnitude. The two aims in the proposal will test both hypotheses. Aim 1 will investigate use of GO to clear water-soluble toxins from plasma, while Aim 2 will investigate the clearance of albumin-bound toxins via albumin dialysis and adsorption to a GO laminate stack. Success in these aims will enable novel device design and treatment flexibility that may include wearable and more efficient therapies with higher quality of life for patients with kidney and liver disease.

摘要 患有终末期肾脏和肝脏疾病以及急性器官衰竭的患者无法维持 需要清除毒素，并需要血液净化技术或器官移植。超过 在美国，40万名终末期肾病（ESRD）患者接受定期血液透析（HD）治疗。 美国的一小部分人接受人工肝支持治疗以解毒和肝脏 失败这些血液净化技术给我们的医疗带来了极高的经济负担。 系统有时效率可疑，生活质量相对较差。ESRD单独治疗 占所有医疗保险支出的7%（310亿美元）。膜和吸附技术落后 在过去的几十年里，这些治疗方法的发展缓慢，限制了制造 重大改进。氧化石墨烯（GO）有可能从根本上改善和改变 血液透析和肝脏支持系统，因为GO双层是最薄的可能分子 筛和纳米级间隔GO堆叠提供了无与伦比的吸附能力。科学前提 在使用GO纳米工程层压板清除水溶性和白蛋白的背后， 结合毒素是双重的首先，先前的工作已经证明，使用纳米多孔材料， 膜使实验室规模的透析器减少了两个数量级， 由于显著增加的渗透性， 尺寸选择性我们假设GO纳米工程层压膜将进一步减少 基于厚度（<10 nm），所需膜面积至少增加另一个数量级， 增加渗透性。其次，白蛋白结合的毒素传统上使用阴离子- 交换柱或活性炭的多孔基质。纳米间隔的GO层压板提供了 固定体积内的表面积的理论极限可能超过常规吸附剂 材料的数量级。提案中的两个目标将检验这两个假设。目标1将 研究使用GO从血浆中清除水溶性毒素，而Aim 2将研究 通过白蛋白透析和吸附到GO层压堆叠来清除白蛋白结合的毒素。 这些目标的成功将使新的设备设计和治疗的灵活性，可能包括 可穿戴和更有效的治疗，为肾脏和肝脏患者提供更高的生活质量 疾病