Use of a Nitric Oxide-Loaded Gel to Improve Healing Outcomes of Burn Injuries

描述：在全球范围内，估计每年有32.2万人死于与火灾有关的烧伤。在美国，45万人经历过需要住院治疗的烧伤，其中3500人导致了致命的后果。烧伤面积占全身面积的30%，最初的住院费用可能高达20万美元，这还不包括因重建和康复而再次入院的额外费用。这些伤害的经济影响远远超出了国家医疗保健系统的成本，还包括工资损失、与残疾有关的成本和情感创伤。本应用程序的主要目的是评估Novan的一氧化氮（NO）释放外用凝胶制剂对热和化学烧伤的疗效。Novan认为，这项研究将证明，局部应用一氧化氮提供了一种突破性的基于人体伤口修复自然过程的再生医学策略。一氧化氮在体内已被证明可以减少炎症，促进新血管的形成，并促进肉芽组织的形成。不幸的是，与一氧化氮的储存和控制递送相关的挑战限制了以一氧化氮为基础的局部治疗的发展。诺万公司的一氧化氮释放二氧化硅纳米颗粒技术（二氧化氮）克服了与其他一氧化氮储存方法相关的输送问题。具体来说，Novan旨在测试Novan的铅无水局部凝胶配方在混合二度烧伤伤口模型中，该模型由美国陆军军事化学防御研究所开发，并通过组织学和生物物理技术量化再上皮化和炎症的比率；并探索无水凝胶在5至40℃温度条件下的稳定性，评估降解产物的效力和定量作为时间和温度的函数。这项为期6个月的I期SBIR拨款的结果将提供热和硫芥（HD）烧伤局部应用一氧化氮愈合效果的比较数据。这一结果将是第一次在体内应用一氧化氮来减轻HD损伤，也是第一次研究一氧化氮在热烧伤中的作用。在II期，Novan将进一步确定一氧化氮与热/HD伤口愈合进展之间的剂量-反应关系，并探索一氧化氮为基础的治疗的完整皮肤毒理学/药代动力学。

DESCRIPTION: Globally, an estimated 322,000 individuals die from fire-related burn injuries each year. In the United States, 450,000 experience burns requiring hospitalization and 3,500 of these lead to fatal outcomes. A burn of 30% of total body area can cost as much as $200,000 in initial hospitalization costs, not including the additional costs for repeat admission for reconstruction and for rehabilitation. The economic impact of these injuries extends far beyond the cost on the nation's healthcare system to include loss of wages, costs relating to deformities, and emotional trauma. The primary goal of this application is to evaluate the efficacy of Novan's nitric oxide (NO)-releasing topical gel formulation against thermal and chemical burns. Novan believes this research will demonstrate that topically applied nitric oxide provides a breakthrough regenerative medicine strategy based on the body's natural process of wound repair. Nitric oxide has been shown in the body to reduce inflammation, promote new blood vessel formation, and facilitate granulation tissue formation. Unfortunately, the challenges associated with the storage and controlled delivery of nitric oxide has limited the development of NO-based topical therapeutics. Novan Inc.'s NO- releasing silica nanoparticle technologies (Nitricil) overcomes the delivery issues associated with other nitric oxide storage methods. Specifically Novan aims to test Novan's lead anhydrous topical gel formulation in a hybrid second-degree burn wound model, developed by United States Army Military Research Institute for Chemical Defense, and quantify the rates of re-epithelialization and inflammation via histological and biophysical techniques; and explore the stability of the anhydrous gel at temperature conditions ranging from 5 to 40 C, assessing both potency and quantification of degradation products as a function of time and temperature. The outcome of this 6-month Phase I SBIR grant will provide comparative data on the healing benefits of topically applied nitric oxide in thermal and sulfur mustard (HD) burns. The results will be the first in vivo application of nitric oxide to mitigate HD injury and the first study of Nitricil in thermal burns.In Phase II, Novan will further define the dose-response relationship between nitric oxide and the thermal/HD wound healing progression, as well as, explore the full dermal toxicology/pharmacokinetics of the NO-based therapy. PUBLIC HEALTH RELEVANCE: Globally, an estimated 322,000 individuals die from fire-related burn injuries each year. In the United States, 450,000 individuals seek medical care each year for burns. Approximately 45,000 experience burns requiring hospitalization and 3,500 of these lead to fatal outcomes. The economic impact of these injuries extends far beyond the cost on the nation's healthcare system to include loss of wages; costs relating to deformities; and emotional trauma. The use of exogenous nitric oxide therapy for the mitigation of burn injuries is extraordinarily promising. Novan believes this research will demonstrate that topically applied nitric oxide reduces burn wound inflammation and accelerates re-epithelialization, providing a regenerative medicine strategy based on the body's natural process of wound repair.