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Drug containing hydrogels which release nitric oxide for diabetic wound healing

含有药物的水凝胶可释放一氧化氮以促进糖尿病伤口愈合

基本信息

批准号：
8901371
负责人：
Tsvetelina Ivanonova Lazarova
金额：
$ 15.18万
依托单位：
MEDCHEM PARTNERS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2016-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8901371
关键词：
Air Amputation Animal Model Animal Testing Animals Biological Assay Blood Vessels Caring Cell Proliferation Chemicals Cicatrix Cleaved cell Collagen Deposition Development Diabetes Mellitus Diabetic ulcer Diabetic wound Dose Drug Formulations Enzymes Equipment Evaluation Exposure to Exudate Fibroblasts Foot Ulcer Gases Gel Generations Goals Granulation Tissue Health Care Costs Human Hydrogels Infection Injury Kinetics Libraries Life Lower Extremity Matrix Metalloproteinases Modeling Myofibroblast Nature Nitric Oxide Performance Pharmaceutical Preparations Phase Plasma Population Process Production Protein Isoforms Protocols documentation Quality of life Rattus Recurrence Research Support Skin Smooth Muscle Actin Staining Method Societies Sterile coverings Streptozocin System Testing Therapeutic Thick Tissue Sample Tissues Toxic effect Ulcer United States Work Wound Healing analog antimicrobial cost db/db mouse density diabetic diabetic wound healing dosage esterase in vivo in vivo Model interest mouse model novel pressure prevent product development productivity loss prototype public health relevance skin irritation small molecule wound

项目摘要

DESCRIPTION (provided by applicant): The goal of this Phase I proposal is to discover and develop compounds which can release a therapeutically relevant amount of nitric oxide in a controllable manner, formulate them into a hydrogel wound dressing, and demonstrate their ability to promote the healing of diabetic wounds in an in vivo model. To date, development of nitric oxide for these purposes has been hampered by the inability to stably sequester nitric oxide and release it in a controlled and selective way. Traditional treatment with gaseous nitric oxide is impractical due to the cumbersome high pressure gas tanks needed. The work undertaken in this project will: (i) identify novel compounds which stably sequester nitric oxide and only release it when they come in contact with a wound; (ii) formulate these into a suitable hydrogel for delivery to the wound and (iii) identify the proper kinetics of release needed to deliver the appropriate dose of nitric oxide to the wound in vivo. We will prepare several small libraries of compounds (36-45 analogs in total) which release nitric oxide at varying rates when exposed to plasma. These compounds will also be assayed for nitric oxide release, formulated into hydrogels, and tested in a mouse model of diabetic wound healing.

描述（由申请人提供）：本I期提案的目标是发现和开发能够以可控方式释放治疗相关量的一氧化氮的化合物，将其配制成水凝胶伤口敷料，并证明其在体内模型中促进糖尿病伤口愈合的能力。迄今为止，用于这些目的的一氧化氮的开发受到不能稳定地螯合一氧化氮并以受控和选择性的方式释放它的阻碍。由于需要笨重的高压气罐，用气态一氧化氮的传统治疗是不切实际的。在这个项目中进行的工作将：（i）确定新的化合物，稳定地隔离一氧化氮，只有当它们与伤口接触时才释放它;（ii）将这些配制成合适的水凝胶，用于递送到伤口和（iii）确定释放所需的适当动力学，以在体内向伤口递送适当剂量的一氧化氮。我们将准备几个小的化合物库（总共36-45个类似物），当暴露于血浆时，这些化合物以不同的速率释放一氧化氮。这些化合物也将被测定一氧化氮释放，配制成水凝胶，并在糖尿病伤口愈合的小鼠模型中进行测试。