Surface-covering gels for broad-spectrum antimicrobial protection following open

描述（由申请人提供）：估计所有骨折中约有3-4%为开放性骨折，其中骨折通过皮肤和软组织缺损暴露。这相当于美国每年约有25万例开放性骨折。开放性骨折感染的风险很高。感染给患者和医疗保健系统造成相当大的经济负担，需要重复手术（通常不止一次），并可能导致骨折延迟愈合或骨不连。对于许多开放性骨折，没有合适的选择用于局部抗菌剂输送。具有快速降解时间的生物相容性局部递送载体可以提供比可用材料更广泛的开放性骨折的有效覆盖。这种技术将为患者和医疗保健提供者提供真实的益处。 预防开放性骨折后感染的一种有希望的方法是使用可吸收的控释载体SB凝胶来持续释放抗菌药物。这些新型凝胶提供了以下改善感染预防的优势：1）持续和完全的抗生素释放; 2）柔软但有粘性的物理结构，允许完全覆盖伤口和器械表面; 3）快速降解性，允许正常骨愈合，无需取出。 拟议工作的目标是确定和开发一种局部递送产品，该产品在开放性骨折后的整个手术伤口上提供广谱抗菌覆盖。这将通过在生物膜形成之前（和在生物膜形成的早期阶段）杀死微生物来显著降低感染率。为此，将评价SB凝胶中银纳米颗粒和庆大霉素的释放。同时，将确定细菌生物膜对这些药物的敏感性。将评价SB凝胶释放的银纳米颗粒和庆大霉素治疗MRSA骨髓炎的有效性。拟议工作的成功完成将提供关于这些新型抗菌剂负载凝胶的安全性和有效性的关键数据，特别是它们用于预防开放性骨折后感染的数据。这项工作的数据预计将支持商业化的同时努力，并直接导致研究支持FDA药物评价和研究中心的研究新药申请。

DESCRIPTION (provided by applicant): About 3-4% of all fractures are estimated to be open fractures, where the fracture is exposed through defects in the skin and soft tissues. This equates to about 250,000 open fractures in the United States annually. Open fractures present a high risk of infection. Infection results in considerable financial burden to both the patient an healthcare system, requires repeat operations (often more than one), and can cause delayed fracture healing or nonunion. There is no suitable option available for local antimicrobial deliver to many open fractures. A biocompatible local delivery vehicle with a fast degradation time could provide effective coverage to a much wider range of open fractures than possible with available materials. Such a technology would provide a real benefit to patients and healthcare providers alike. A promising approach for preventing infections following open fractures is to use a resorbable controlled release carrier, SB Gel, for the sustained release of antimicrobial drugs. These new gels offer the following advantages for improved prevention of infection: 1) sustained and complete antibiotic release; 2) soft yet cohesive physical structure allowing for complete coverage of wound and device surfaces, and 3) rapid degradability allowing for normal bone healing and without requiring removal. The goal of the proposed work is to identify and develop a local delivery product that provides broad-spectrum antimicrobial coverage over the entire surgical wound following an open fracture. This would significantly reduce infection rates by killing microbes prior to (and in the early stages of) biofilm formation. To do this, the release o silver nanoparticles and gentamicin will be evaluated from SB Gel. In parallel, susceptibility of bacterial biofilms in response to these drugs will be determined. The effectiveness of silver nanoparticles and gentamicin released from SB Gel in the treatment of MRSA osteomyelitis will be evaluated. Successful completion of the proposed work will provide critical data regarding the safety and effectiveness of these novel antimicrobial-loaded gels, and in particular their use to prevent infection following open fractures. Data from this work is expected to support concurrent efforts toward commercialization and lead directly to studies supporting an Investigational New Drug application to FDA's Center for Drug Evaluation and Research.