Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium

含银镓的超薄可溶性抗菌膜伤口接触敷料

基本信息

批准号：
9621893
负责人：
Ankit Agarwal
金额：
$ 22.5万
依托单位：
IMBED BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-18 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9621893
关键词：
Address Advanced Development Animals Antibiotics Antimicrobial Resistance Bacteria Beds Biocompatible Materials Biological Sciences Biopsy Caring Chronic Clinical Clinics and Hospitals Complex Data Debridement Discipline of Nursing Economics Evaluation Family suidae Formulation Gallium Goals Government Growth Health Care Costs Healthcare Hybrids Impaired wound healing In Vitro Ions Legal patent Length of Stay Metabolism Microbe Microbial Biofilms Microbiology Microfilm Modeling Mus Names Organism Pain Patients Persons Phase Polymers Preparation Pseudomonas aeruginosa Recrudescences Recurrence Research Research Personnel Research Project Grants Resistance Silver Small Business Innovation Research Grant Source Splint Device Staphylococcus aureus Sterile coverings Surface Technology Testing Therapeutic Time Tissues Transition Elements Treatment Cost Treatment Efficacy Visit Wound Infection antimicrobial antimicrobial drug base chronic wound cost effective cytotoxicity design experimental study healing in vivo evaluation microbial nanoparticle next generation phase 2 study prevent prototype standard of care synergism wound wound closure

项目摘要

The entire Research Plan contains proprietary/privileged information that Imbed Biosciences requests not be released to persons outside the Government, except for purposes of review and evaluation. Title: Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium Summary The health care costs associated with treatment of chronic and burn wounds exceeds $25 billion annually in the U.S. Biofilms are implicated as a key factor responsible for delayed healing in chronic wounds. Many wounds have complex surfaces and debridement can be challenging, leaving biofilm fragments that remain resistant to antimicrobial therapy and act as a nidus for recrudescence of biofilms. This underscores the unmet need for a cost-effective and non-cytotoxic antibiofilm wound dressing. There is currently no commercially available wound dressing that is clinically indicated for dispersal of biofilms in a wound bed. Imbed Biosciences Inc. has developed and commercialized a unique microfilm wound contact dressing with silver nanoparticles, named MicroLyte Ag, based on its patented polymeric multilayer nanofilm technology, that conforms to the micro-contours of a wound bed, provides an intimate and sustained contact of active agents with the wound bed, and requires 100x lower concentration of silver ions (compared to conventional dressings) to achieve therapeutic efficacy without cytotoxicity. MicroLyte Ag is highly effective in killing planktonic bacteria and has demonstrated efficacy in suppression of biofilm formation. However, the next challenge is to create a wound dressing that will stimulate dispersal of established biofilms in wounds. Our preliminary data shows that Ag+ and Ga3+ biofilm, when delivered through polyelectrolyte multilayer nanofilm, achieved 1000x greater reduction in biofilm CFU than a corresponding topical formulation. This research project will test the hypothesis that sensitization of microbes in biofilms by antibiofilm gallium would enable non-cytotoxic levels of antimicrobial silver to kill biofilm-encased bacteria. There is currently no commercial wound dressing or topical formulation that employs gallium as an antibiofilm agent. Our preliminary experiments have shown that MicroLyte Ag-Ga prototypes can achieve up to 4 Log10 CFU reduction in 48 h old P. aeruginosa biofilms and disperse ≥ 90% of biofilm mass in vitro, despite releasing 5-10x lower levels of Ag+ than commercial antimicrobial dressings that did not exhibit any significant antibiofilm activity. This proposal seeks to advance development of a next-generation antimicrobial-antibiofilm wound dressing containing silver and gallium. The goal of this Phase 1 feasibility research is to: (AIM 1) Identify silver and gallium loadings in MicroLyte Ag-Ga that exert antibiofilm activity against single and multispecies biofilms of P. aeruginosa and S. aureus without in vitro cytotoxicity and, (AIM 2) Evaluate efficacy of MicroLyte Ag-Ga in dispersal of preformed biofilms in splinted murine wounds. For this project, Imbed has assembled a team of researchers with substantial expertise in biomaterials (Agarwal, Dalsin, Pranami, and Abbott), microbiology (Czuprynski), animal wound models (McAnulty) and clinical wound care (McAnulty and Schurr). Successful completion of Phase 1 research will provide feasibility data for a Phase 2 project to study dispersal of biofilms of multiple bacterial strains in murine/porcine wound models.

整个研究计划包含 Imbed Biosciences 要求不得向他人透露的专有/特权信息政府以外的范围，但出于审查和评估目的除外。标题：含银和镓的超薄可溶性抗菌膜伤口接触敷料概括每年与治疗慢性和烧伤伤口相关的医疗保健费用超过 250 亿美元美国生物膜被认为是导致慢性伤口愈合延迟的关键因素。伤口具有复杂的表面，清创可能具有挑战性，留下生物膜碎片对抗菌治疗产生耐药性并成为生物膜复发的病灶，这凸显了尚未得到满足的问题。需要一种具有成本效益且无细胞毒性的抗生物膜伤口敷料目前还没有商业化的敷料。临床上适用于在伤口床中分散生物膜的可用伤口敷料。 Biosciences Inc. 开发并商业化了一种独特的含银微胶片伤口接触敷料名为 MicroLyte Ag 的纳米粒子，基于其获得专利的聚合物多层纳米膜技术，符合伤口床的微轮廓，提供活性剂的紧密且持续的接触与伤口床一起使用，并且需要的银离子浓度低 100 倍（与传统敷料相比） MicroLyte Ag 能够高效杀死浮游细菌，从而达到治疗效果。并已证明具有抑制生物膜形成的功效。然而，下一个挑战是创造一种我们的初步数据表明，伤口敷料将刺激伤口中已形成的生物膜的扩散。 Ag+ 和 Ga3+ 生物膜通过聚电解质多层纳米膜传递时，可实现 1000 倍的放大与相应的局部制剂相比，生物膜 CFU 减少了该研究项目将检验这一假设。抗生物膜镓对生物膜中微生物的敏化将使非细胞毒性水平的抗菌银可以杀死生物膜包裹的细菌，目前还没有商业化的伤口敷料或。我们的初步实验表明，使用镓作为抗生物膜剂的局部制剂。 MicroLyte Ag-Ga 原型可以在 48 小时的铜绿假单胞菌生物膜中实现高达 4 Log10 CFU 的减少尽管释放的 Ag+ 水平比商业产品低 5-10 倍，但在体外可分散 ≥ 90% 的生物膜质量该提案旨在推动未表现出任何显着抗生物膜活性的抗菌敷料。开发含有银和的下一代抗菌抗生物膜伤口敷料第一阶段可行性研究的目标是：（目标 1）确定银和镓的含量。 MicroLyte Ag-Ga 对铜绿假单胞菌和金黄色葡萄球菌的单一和多物种生物膜发挥抗生物膜活性。无体外细胞毒性的金黄色葡萄球菌，(AIM 2) 评估 MicroLyte Ag-Ga 在预形成的分散中的功效在这个项目中，Imbed 组建了一个研究小组，在生物材料（Agarwal、Dalsin、Pranami 和 Abbott）、微生物学（Czuprynski）、动物学方面拥有丰富的专业知识伤口模型 (McAnulty) 和临床伤口护理 (McAnulty 和 Schurr) 成功完成第一阶段。研究将为研究多种细菌生物膜分散的第二阶段项目提供可行性数据鼠/猪伤口模型中的菌株。