Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules

扰动细胞外结构促进生物大分子的吸收和淋巴转运

• 批准号: LP140100377
• 负责人: Prof Chris Porter
• 金额: $ 28.85万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: Linkage Projects
• 财政年份: 2015
• 资助国家: 澳大利亚
• 起止时间: 2015-01-06 至 2018-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/LP140100377
• 关键词: Perturbation; extracellular; architecture; promote; absorption

Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote absorption into the draining blood and lymph capillaries. The project aims to also explore the downstream effects of hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph node structure and promote drug penetration into the lymph node mass. This has significant potential for improved drug targeting.

大分子治疗剂如蛋白质、抗体或聚合物缀合物提出了许多药学挑战。在剂量高的情况下，该剂量从皮下注射部位排出到循环中造成了特别的问题。在这里，该项目旨在探索如何重组透明质酸酶，一种分解组织结构成分（透明质酸）的酶，可用于促进吸收到引流血液和淋巴毛细血管。该项目还旨在探索透明质酸酶对淋巴结的下游影响，并评估该酶是否能够暂时破坏淋巴结结构并促进药物渗透到淋巴结肿块中。这对于改进药物靶向具有显著的潜力。