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.

概括 糖尿病患者的伤口愈合受损是一个主要的临床问题，导致长期 住院治疗和巨额医疗支出造成的经济负担是巨大的。 仅在美国，每年就有三分之二的非创伤性截肢手术是由糖尿病患者造成的。 糖尿病伤口愈合不良，每 20 秒就会失去一个下肢。 是多因素造成的，但主要的致病特征是慢性炎症，这些可怕的、容易感染的溃疡。 使用当前技术很难治疗，并且代表了市场上严重未满足的需求。 目前针对这些病症常用的治疗方法包括标准绷带或碱性水凝胶 它们有很多问题，包括引起炎症反应，需要去除并 经常改变，并且不能持续释放药物，GelSana Therapeutics, Inc. 正在解决这个问题。 需要其伤口愈合水凝胶，可以帮助伤口明显更快地愈合，并且无需 当今敷料的缺点是凝胶基于聚合物，会排斥蛋白质吸附并防止蛋白质吸附。 此外，研究表明此类材料具有抗炎作用。 对于伤口愈合能力受损的糖尿病小鼠，GelSana 证明，单独使用水凝胶 将愈合时间缩短至盐水处理糖尿病伤口时间的 2/3，与 这表明该材料本身就可以纠正糖尿病对伤口愈合的损害。 GelSana 材料也已被证明优于市售中使用的另一种类型的水凝胶 这些糖尿病小鼠伤口愈合所需的产品此外，水凝胶还含有一种成分。 在这个项目中，GelSana 专有的抗炎药物将愈合时间缩短了一半。 两性离子水凝胶将作为优质伤口敷料材料，帮助纠正糖尿病伤口 通过减少炎症来治疗损伤，从这些敷料中持续输送 IL-10 将 进一步解决糖尿病患者伤口环境中的慢性炎症并改善 血管化，从而使糖尿病溃疡以与非糖尿病溃疡相同或更快的速度愈合 该第一阶段项目将证明 GelSana 两性离子的可行性。 通过 (1) 表征体外药物释放和生物活性以及 (2) 评估含有和不含 IL-10 的水凝胶 体内小鼠糖尿病溃疡模型中的功效 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：量化其影响。 药物的持续释放对药物装置产品改善伤口愈合的能力的影响 这项工作将产生一种新型的抗炎促再生水凝胶伤口。 持续释放对抗氧化应激和炎症的新型疗法的敷料 促进糖尿病伤口的血管生成，以治疗性地减少炎症、缩短愈合时间，以及 提高组织修复质量。