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

在全球范围内，估计每年有322，000人死于与火灾有关的烧伤。在美国，有45万人经历了需要住院治疗的烧伤，其中3,500人导致了致命的后果。烧伤总面积的30%可能会花费高达20万美元的初始住院费用，不包括重建和康复的重复入院的额外费用。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，包括工资损失，与畸形有关的成本和情感创伤。本申请的主要目的是评价Novan的一氧化氮（NO）释放局部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个突破性的再生医学策略的基础上，身体的自然过程的伤口修复。一氧化氮已被证明在体内减少炎症，促进新血管形成，并促进肉芽组织形成。不幸的是，与一氧化氮的储存和受控递送相关的挑战限制了基于NO的局部治疗剂的发展。Novan Inc.的NO释放二氧化硅纳米颗粒技术（Nitricil）克服了与其他一氧化氮储存方法相关的输送问题。具体而言，Novan旨在测试Novan的铅无水局部凝胶制剂在美国陆军化学防御军事研究所开发的混合二度烧伤伤口模型中的作用，并通过组织学和生物物理学技术量化上皮再生和炎症的速率;并探索无水凝胶在5 - 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个月的第一阶段SBIR资助的结果将提供关于局部应用一氧化氮在热烧伤和硫芥（HD）烧伤中的愈合益处的比较数据。该研究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Nitricil在热烧伤中的作用。在第二阶段，Novan将进一步确定一氧化氮与热/HD伤口愈合进程之间的剂量反应关系，以及探索基于NO的治疗的完整皮肤毒理学/药代动力学。 公共卫生相关性：在全球范围内，估计每年有322，000人死于与火灾有关的烧伤。在美国，每年有45万人因烧伤寻求医疗护理。大约45，000人经历了需要住院治疗的烧伤，其中3，500人导致致命后果。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，包括工资损失;与畸形有关的费用;和情感创伤。使用外源性一氧化氮治疗减轻烧伤是非常有前途的。Novan认为这项研究将证明， 应用一氧化氮减少烧伤伤口炎症并加速上皮再生，提供了一种基于身体自然伤口修复过程的再生医学策略。

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.