Topical Drug Delivery System as an Anti-Inflammatory and Pro-Angiogenic Therapy for Diabetic Wound Healing

局部给药系统作为糖尿病伤口愈合的抗炎和促血管生成疗法

• 批准号: 10696266
• 负责人: Adam Rocker
• 金额: $ 29.97万
• 依托单位: GELSANA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-24 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696266
• 关键词: Address; Adsorption; Amputation; Animals; Anti-Inflammatory Agents; Bandage; Bolus Infusion; Charge; Chronic; Clinical; Colorado; Devices; Diabetic mouse; Drug Combinations; Drug Delivery Systems; Financial Hardship; Foreign Bodies; Formulation; Gel; Goals; Health Expenditures; Hospitalization; Hydrogels; Immune response; Impaired healing; Impaired wound healing; Impairment; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Injections; Interleukin-10; Licensing; Lower Extremity; Macrophage; Modeling; Mus; Oxidative Stress; Oxygen; Pathogenicity; Pathway interactions; Pharmaceutical Preparations; Phase; Phenotype; Polymers; Property; Proteins; Saline; Schools; Sterile coverings; Technology; Therapeutic; Time; Ulcer; Vascularization; Vertebral column; Work; angiogenesis; combat; common treatment; cytokine; diabetic; diabetic patient; diabetic ulcer; diabetic wound healing; efficacy evaluation; healing; immunoregulation; improved; in vivo; learning materials; mouse model; non-diabetic; novel therapeutics; prevent; professor; regenerative; response; standard of care; tissue repair; wound; wound bed; wound dressing; wound environment; wound healing; wound treatment

SUMMARY Impaired wound healing in diabetic patients represents a major clinical problem, resulting in prolonged hospitalizations and significant healthcare expenditures. The financial burden of this is extreme, representing $78 billion annually in the U.S. alone. Two-thirds of all non-traumatic amputations are preceded by a diabetic wound, and every 20 seconds a lower limb is lost to a diabetic wound. The impaired healing of diabetic wounds is multifactorial, but a central pathogenic feature is chronic inflammation. These terrible, infection-prone ulcers are difficult to treat using current technologies and represent a significant under-met need in the marketplace. Current treatments commonly employed for these conditions involve standard bandages or basic hydrogels which have many drawbacks, including that they cause inflammatory response, need to be removed and changed often, and are not capable of sustained drug release. GelSana Therapeutics, Inc. is addressing this need with its proprietary wound healing hydrogels that help heal wounds significantly faster and without the downsides of today’s dressings. The hydrogels are based on polymers that repel protein adsorption and prevent the foreign body response. Further, this class of materials have been shown to be anti-inflammatory. In studies with diabetic mice with impaired wound healing abilities, GelSana has demonstrated that the hydrogels alone cut the healing time down to 2/3 of the time of saline-treated diabetic wounds, matching the healing time of healthy mice. This indicates that the material alone can correct the diabetic impairment to wound healing. GelSana materials have also been shown to outperform another type of hydrogel used in commercially available products in the time of healing required for these diabetic murine wounds. Furthermore, hydrogels laden with an anti-inflammatory drug cut the healing time down by a staggering one-half. In this project, GelSana proprietary zwitterionic hydrogels will serve as superior wound dressing materials to aid in correcting the diabetic wound healing impairment by reducing inflammation, where sustained delivery of IL-10 from these dressings will be demonstrated to further resolve chronic inflammation in the diabetic wound environment and improve vascularization, thus allowing the diabetic ulcer to heal at a rate equivalent to or faster than that found in non- diabetic (healthy) saline-treated wounds. This Phase I project will demonstrate feasibility for GelSana zwitterionic hydrogels with and without IL-10 by (1) characterizing drug release and bioactivity in vitro and (2) assessing efficacy in an in vivo murine diabetic ulcer model. This will be accomplished with these Aims: Aim 1: To quantify the release rate and bioactivity of IL-10 from zwitterionic hydrogels. Aim 2: To quantify the impact of sustained release of the drug on the ability of the drug-device product to improve wound healing in a murine model. This work will result in a new class of anti-inflammatory pro-regenerative hydrogel wound dressings with sustained release of novel therapeutics that combat oxidative stress and inflammation and promote angiogenesis in diabetic wounds to therapeutically decrease inflammation, decrease healing time, and increase tissue repair quality.

摘要 糖尿病患者的伤口愈合受损是一个主要的临床问题，导致延长 住院和巨额医疗支出。这带来的财政负担是极端的，代表着 仅在美国，每年就有780亿美元。在所有非创伤性截肢手术中，有三分之二的患者是糖尿病患者。 每20秒就有一条小腿因糖尿病伤口而失去。糖尿病创面愈合受阻 是多因素的，但一个主要的致病特征是慢性炎症。这些可怕的、容易感染的溃疡 使用目前的技术很难治疗，并且代表着市场上严重未得到满足的需求。 目前通常用于这些疾病的治疗方法包括标准绷带或基本水凝胶。 有许多缺点，包括它们会引起炎症反应，需要移除和 经常改变，不能持续释放药物。GelSana治疗公司正在解决这一问题 需要其专有的伤口愈合水凝胶，帮助伤口愈合得更快，而不需要 今天的调味品的缺点。这种水凝胶是以聚合物为基础的，这种聚合物可以排斥蛋白质的吸附并防止 异物反应。此外，这类材料已被证明是抗炎的。在研究中 在伤口愈合能力受损的糖尿病小鼠身上，GelSana已经证明了仅水凝胶 将愈合时间缩短至盐水治疗糖尿病伤口的三分之二，与糖尿病伤口的愈合时间相当 健康的老鼠。这表明，该材料本身可以纠正糖尿病对伤口愈合的损害。 GelSana材料也被证明比商业上使用的另一种水凝胶性能更好 在这些糖尿病小鼠伤口愈合时所需的产品。此外，水凝胶中含有一种 消炎药将愈合时间缩短了惊人的一半。在这个项目中，GelSana拥有 两性离子水凝胶将作为优良的伤口敷料材料，帮助纠正糖尿病伤口。 通过减少炎症来修复损伤，从这些敷料中持续释放IL-10将是 证明能进一步消除糖尿病伤口环境中的慢性炎症并改善 血管化，从而使糖尿病溃疡的愈合速度与非糖尿病患者相同或更快 糖尿病(健康)生理盐水处理的伤口。该第一阶段项目将论证GelSana zwitterion的可行性 含和不含IL-10的水凝胶：(1)体外药物释放和生物活性的表征；(2)评价 体内糖尿病小鼠溃疡模型的疗效。这将通过以下目标来实现：目标1：量化 两性离子水凝胶中IL-10的释放速率和生物活性。目标2：量化以下项目的影响 药物缓释对药物装置产品促进伤口愈合能力的影响 小鼠模型。这项工作将产生一种新型的抗炎促再生水凝胶伤口 具有持续释放的新疗法的敷料，该疗法可对抗氧化应激和炎症，并 促进糖尿病创面的血管生成，从治疗上减少炎症，缩短愈合时间，以及 提高组织修复质量。