A replenishable LIS coating that eliminates occlusion and reduces infection on vascular catheters

可补充的 LIS 涂层可消除血管导管的闭塞并减少感染

• 批准号: 10872872
• 负责人: Zheng Zhang
• 金额: $ 0.65万
• 依托单位: LIQUIGLIDE, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10872872
• 关键词: Achievement; Animals; Antimicrobial Resistance; Blood Vessels; Catheter-related bloodstream infection; Catheters; Complication; Cyclic GMP; Device Removal; Devices; FDA approved; Healthcare; Implant; In Vitro; Infection; Injections; Investigation; Legal patent; Liquid substance; Microbial Biofilms; Monitor; Morbidity - disease rate; Nutrient; Parenteral Nutrition; Pathway interactions; Performance; Peripheral; Phase; Process; Safety; Side; Surface; Thrombosis; Thrombus; Venous; antimicrobial drug; clinical efficacy; cost; healing; implantation; in vivo; intravenous administration; meetings; microbial; microorganism; mortality; novel; phase 1 study; porcine model; pre-clinical; premature; prevent; product development; scale up; surface coating; thrombogenesis

PROJECT SUMMARY Catheter-related bloodstream infection (CRBSI) is a leading cause of healthcare-acquired infections (HAIs) and is associated with high mortality (12–25%) and cost ($9 billion in the US). Catheter-related thrombosis (CRT) is another common complication with central venous catheters (CVCs) that contributes to 41% of premature device removal before treatment is over. Although various coatings, including those with anti-thrombogenic or antimicrobial agents have been applied, the safety and clinical efficacy of these coatings to reduce the rates of CRBSI and/or CRT remains unsatisfactory, especially for extended implantation. LiquiGlide is investigating a new coating solution to overcome the limitations. Liquid-impregnated surface (LIS) provides a non-adherent, self-healing, and replenishable surface that other coatings cannot achieve. Formulating a LIS coating with parenteral nutrient ingredients that have been approved by FDA for intravenous administration, confirming their safety, we have developed a coated surface that significantly reduces thrombus formation and bacterial colonization. When the coating is applied on a vascular catheter, the parenteral nutrients can be replenished through the catheter lumen to increase the duration of efficacy, which is especially beneficial as occlusion and long-term CRBSI occur predominantly through the intralumenal pathway. In preliminary studies, we demonstrated the safety and patency of coated catheters in a swine model during an implantation with three replenishments. The objective of this proposal is to develop the LIS coating on a peripherally inserted central catheter (PICC) to eliminate occlusion and reduce infection in long-term implantation with a side-by-side comparison in a same animal. To achieve the objective, we will first apply the coating on a PICC, meeting the safety and durability requirements as a vascular implant. Then, the LIS-coated PICC will be evaluated in vitro to assess its ability to prevent thrombosis formation (>95% reduction) and achieve 100% elimination of occlusion (Aim 1) under simulated external flow and infusate injections. We will further demonstrate that the coated device has a broad spectrum anti-microbial resistance (Aim 2), targeting reducing both bacterial colonization and biofilm formation with >99% reduction with three typical microorganisms that commonly cause CRBSI. To evaluate the safety and anti-occlusion/anti-infection efficacy in vivo, we will perform a seven-animal study with a swine model, monitoring catheter patency and microorganism colonization on the devices during implantation and assessing explants for thrombus formation and microbial cultures/identification (Aim 3). The proposed phase I study will address challenges related to replenishable LIS-coated PICCs, achieving full occlusion elimination and significant CRBSI reduction. Upon achievement of the phase I milestones, the coated PICC will be ready for the next level of product development. The next phase will target at scaling-up the coating process with LiquiGlide in-house cGMP facility, preforming confirmatory preclinical investigation for regulatory submission, and being ready to product launch.

项目概要 导管相关血流感染 (CRBSI) 是医疗保健获得性感染 (HAIs) 和 与高死亡率（12-25%）和费用（美国 90 亿美元）相关。 中心静脉导管 (CVC) 的另一种常见并发症，导致 41% 的装置过早出现 尽管有各种涂层，包括具有抗血栓形成或抗凝血作用的涂层，但在治疗结束之前应将其去除。 抗菌剂的应用，这些涂层的安全性和临床功效，以降低感染率 CRBSI 和/或 CRT 仍然不能令人满意，特别是 LiquiGlide 正在研究延长植入。 新的涂层解决方案克服了液体浸渍表面（LIS）的局限性。 配制 LIS 涂层无法实现的自修复和可补充表面。 经 FDA 批准用于静脉注射的肠外营养成分，确认其 为了安全，我们开发了一种涂层表面，可显着减少血栓形成和细菌 当将涂层涂在血管导管上时，可以补充肠外营养物质。 通过导管腔以增加疗效的持续时间，这对于闭塞和 在初步研究中，长期 CRBSI 主要通过腔内途径发生。 证明了在猪模型中植入三个涂层导管的安全性和通畅性 该提案的目的是在外周插入的中心上开发 LIS 涂层。 并排植入导管（PICC）可消除闭塞并减少长期植入时的感染 为了实现这一目标，我们首先将涂层涂在 PICC 上，以满足要求。 然后，对 LIS 涂层 PICC 进行体外评估，以评估其作为血管植入物的安全性和耐久性要求。 评估其预防血栓形成（减少>95%）并实现100%消除闭塞的能力 （目标 1）在模拟外部流动和输液注射下我们将进一步证明涂层装置。 具有广谱抗微生物耐药性（目标 2），旨在减少细菌定植和生物膜 三种通常引起 CRBSI 的典型微生物的形成率降低了 >99%。 体内安全性和抗闭塞/抗感染功效，我们将用猪模型进行七种动物研究， 在植入和评估过程中监测导管的通畅性和设备上的微生物定植 外植体用于血栓形成和微生物培养/鉴定（目标 3）。 解决与可补充的 LIS 涂层 PICC 相关的挑战，实现完全闭塞消除和 在实现第一阶段里程碑后，涂层 PICC 将为 CRBSI 显着减少做好准备。 下一阶段的产品开发目标是扩大 LiquiGlide 的涂层工艺。 内部 cGMP 设施，为监管提交进行确认性临床前调查，并正在 准备推出产品。