A Nitric Oxide Polymer Platform for the Prevention and Treatment of Infected Wounds

用于预防和治疗感染伤口的一氧化氮聚合物平台

• 批准号: 9347940
• 负责人: Nina Bionda
• 金额: $ 25.58万
• 依托单位: IFYBER, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347940
• 关键词: Acute; Address; Advanced Development; Animals; Anti-Bacterial Agents; Antibiotics; Biocide; Biocompatible Materials; Biological Models; Caring; Chronic; Clinical; Data; Data Set; Dermal; Development; Erythema; Exhibits; Family suidae; Florida; Formulation; Foundations; Future; Goals; Granulation Tissue; Health; In Vitro; Infection; Infection prevention; Inflammatory; Inflammatory Response; Laboratories; Lead; Medical; Microbial Biofilms; Modeling; Molecular; Morbidity - disease rate; National Cancer Institute; Nitric Oxide; Patient-Focused Outcomes; Patients; Phase; Pilot Projects; Plague; Polymers; Povidone; Prevention; Process; Property; Prophylactic treatment; Research; Research Design; Series; Skin wound; Small Business Innovation Research Grant; Solid; Sterile coverings; Technology; Test Result; Testing; Topical Antibiotic; Topical application; Universities; Wound Healing; Wound Infection; antimicrobial; base; biomaterial compatibility; chronic wound; combat; design; efficacy testing; healing; improved; improved outcome; in vivo; microbial; phase 2 study; point of care; pre-clinical; prototype; research and development; wound

This proposed SBIR research effort will lay the foundation for commercializing a new class of biomaterial for the prevention and treatment of infected skin wounds, thereby enhancing patient health through improved patient outcome and reduced patient morbidity. Specifically, we will focus on evaluating and developing a biomaterial comprised of a nitric oxide (NO)-releasing based on a commonly used medical polymer. Important to the current application, this polymer can be designed to releases NO at predefined levels and exhibits excellent antibacterial and anti-biofilm properties as evidenced by our preliminary data using both in vitro and ex vivo biofilm models where it significantly outperforms commercially available wound care dressings. Through the completion of research and development tasks during the Phase I/II efforts, we will have compiled a compelling data set that outlines the biocompatibility, the efficacy and the mode of action of the NO-releasing polymer in infection management and wound healing that supports its entry into the FDA's regulatory process. Nitric oxide-releasing technologies offer a compelling alternative to standard antimicrobial treatments and antibiotics currently used in to combat infection in wounds. Our preliminary data clearly demonstrate the potential clinical utility of the proposed NO-releasing polyemr in addressing microbial infection in general, and more importantly, prevention and treatment of microbial biofilms that plague chronic skin wounds. An important milestone for this Phase I project will be the development of prototype NO-releasing topical formulations that will serve as both a non-antibiotic prophylactic treatment against microbial infection and as a treatment for chronically infected wounds – two unmet needs within the wound care field. Completion of the Phase I efforts will result in a compelling data set that outlines the efficacy and defines the minimal requirements for product formulation in terms of topical application. Together, these studies will help in the transition to broader Phase II studies designed to support entry of our product into the FDA's regulatory process. iFyber will address the efficacy of the NO-releasing technology through the Phase I aims and tasks outlined below: AIM 1. Develop a series of prototype topical formulation guided by an ex-vivo dermal model system Task 1. Produce prototype NO-releasing topical formulations. Past R&D efforts have established that point-of-care (POC) compounding is a plausible strategy for an NO-based wound dressing; that is, POC formulation(s) that are mixed just prior to applying to a wound. Prototype formulations selection will be guided by efficacy testing in the ex vivo model (Task 2) and subsequently in pilot in vivo studies (Task 4). Task 2. Conduct ex vivo dermal model testing for formulation selection. The goal of this task is to evaluate the efficacy of the prototype formulations from Task 1 in an ex vivo porcine dermal model to define suitable antimicrobial and anti-biofilm semi-solid dressings for wounds. A main goal in this task will be to down-select formulations for pilot animal studies (Tasks 3 and 4). AIM 2. Guide prototype development through pre-clinical pilot studies Task 3. Conduct in vivo testing on selected formulations. Most promising formulations identified through Task 1-2 will be evaluated in two pilot in vivo studies conducted in the laboratory of Dr. Steven Davis at the University of Miami. These studies will establish efficacy in biofilm prevention (study 1) and reduction in an existing biofilm-associated infection (study 2), and results of these studies will help to further down-select formulations for future Phase II development Task 4. Determine the baseline in vivo biocompatibility profile of the NO-releasing polymer. In addition to assessing infection prevention and anti-biofilm efficacy, the effects of candidate formulations on non-infected wounds will also be assessed with respect to the wound healing process; specifically, inflammatory response, erythema, re-epithelialization, granulation tissue formation, and initial molecular screens for healing and inflammatory processes.

这项拟议的SBIR研究工作将为新型生物材料的商业化奠定基础 预防和治疗感染的皮肤伤口，从而通过改善患者的健康 患者转归和降低患者发病率。具体地说，我们将重点评估和开发一个 由基于常用医用聚合物的一氧化氮(NO)释放组成的生物材料。重要 对于当前的应用，这种聚合物可以被设计成在预定的水平和展品中释放NO 良好的抗菌和抗生物被膜性能，从我们的初步数据证明，在体外和 体外生物膜模型，在那里它的表现明显优于商业上可获得的伤口护理敷料。 通过在第一阶段/第二阶段期间完成研究和开发任务，我们将编制 一个令人信服的数据集，概述了NO释放的生物相容性、有效性和作用模式 感染管理和伤口愈合方面的聚合物，支持其进入FDA的监管程序。 一氧化氮释放技术提供了一种令人信服的替代标准抗菌治疗和 目前用于对抗伤口感染的抗生素。我们的初步数据清楚地表明 建议的NO释放聚EMR在一般情况下解决微生物感染的潜在临床效用，以及 更重要的是，预防和治疗困扰慢性皮肤伤口的微生物生物膜。一个重要的 这个第一阶段项目的里程碑将是开发原型NO释放外用制剂 这既是一种针对微生物感染的非抗生素预防性治疗，也是一种 慢性感染伤口的治疗--伤口护理领域的两项未得到满足的需求。 第一阶段工作的完成将产生一个令人信服的数据集，其中概述了有效性并定义了 在局部应用方面对产品配方的最低要求。总之，这些研究将有助于 过渡到更广泛的第二阶段研究，旨在支持我们的产品进入FDA的监管 进程。IFyber将通过第一阶段的目标和任务来解决NO释放技术的有效性 概述如下： 目的1.在体外皮肤模型系统的指导下，开发一系列原型外用制剂 任务1.制作NO释放外用配方的原型。过去的研发努力已经确立了 护理点(POC)复合对于无基础伤口敷料来说是一种合理的策略；即， POC配方(S)，在涂于伤口之前混合。原型配方选择 将以体外模型(任务2)和随后的体内试验中的有效性测试为指导 (任务4)。 任务2.进行体外真皮模型试验以进行配方选择。这项任务的目标是 评估任务1中的原型配方在体外猪皮肤模型中的有效性 确定适用于伤口的抗微生物和抗生物被膜半固体敷料。这项任务的一个主要目标 将向下选择用于实验动物研究的配方(任务3和4)。 目标2.通过临床前先导研究指导原型开发 任务3.对选定的配方进行体内测试。确定了最有希望的配方 通过任务1-2将在Steven博士的实验室进行的两项试验性活体研究中进行评估 戴维斯在迈阿密大学。这些研究将确定生物被膜预防的有效性(研究1)和 减少现有的生物膜相关感染(研究2)，这些研究的结果将有助于 未来第二阶段开发的进一步精选配方 任务4：确定NO释放聚合物的体内生物相容性基线。在……里面 除了评估感染预防和抗生物被膜的效果外，候选配方的效果 还将根据伤口愈合过程对非感染伤口进行评估；具体地说， 炎症反应、红斑、再上皮化、肉芽组织形成和初始分子 用于治疗和炎症过程的筛查。