Mechanistic evaluation of amino acids as adjuvants in modulating buccal transport of biologicals

氨基酸作为调节生物制品口腔运输佐剂的机制评价

• 批准号: 2596910
• 金额: --
• 依托单位: Aston University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2596910
• 关键词: Mechanistic; evaluation; amino; acids; adjuvants

To be confirmed at end of year 1: MIBTP students undertake a period of training during their first year. This includes compulsory taught modules in statistics, programming, data analysis, AI and mini Research projects.Project confirmed: Biologics, such as proteins and peptides, have massive therapeutic potential, with many proteins being developed for clinical use since first approval of recombinant insulin in 1982. Although a non-invasive route of delivery would be much preferred, parenteral administration remains the predominant delivery route for the majority of therapeutic proteins, e.g. use of subcutaneous insulin in diabetes mellitus. Very few therapeutic proteins have progressed to Phase III clinical trials via the oral route because of its hostile environment, designed for the catabolism of nutrients, completely incompatible with the physiochemical nature of biologics, properties which in turn create difficulties in transportation from the alimentary canal to the systemic circulation. For this reason, research at Aston has focussed on buccal delivery of biologics and it has recently been demonstrated that the transport of insulin across buccal mucosa can be modulated through use of amino acids as adjuvants1. It is now proposed to extend this work to study the use of engineered composite microparticles of biologics coated with amino acids to assist transport across an immortalised buccal cell-line1. It is hypothesized that these coatings will not only conserve biological activity, as has been demonstrated in the laboratory with other functional excipients, but will also modulate uptake through the buccal mucosa. The purpose of the proposed project is to study amino-acid protected composite particles carrying various representative biologics in buccal absorption. In this way, the factors and mechanisms involved in modulating the buccal transport of a range of biologics will be elucidated with the ultimate aim of informing better formulation of such agents and enabling more confident use of this non-invasive delivery route in future biopharmaceutical medicines.

在第一年结束时确认：MIBTP学生在第一年接受一段时间的培训。其中包括统计学、编程、数据分析、人工智能和微型研究项目的必修教学模块。项目确认：蛋白质和肽等生物制剂具有巨大的治疗潜力，自1982年重组胰岛素首次获得批准以来，许多蛋白质已被开发用于临床。尽管非侵入性递送途径将是更优选的，但肠胃外施用仍然是大多数治疗性蛋白质的主要递送途径，例如在糖尿病中使用皮下胰岛素。很少有治疗性蛋白质通过口服途径进展到III期临床试验，因为其不利的环境，设计用于营养素的催化，与生物制剂的理化性质完全不相容，这些性质反过来又造成从消化道运输到体循环的困难。出于这个原因，阿斯顿的研究集中在生物制剂的口腔递送上，并且最近已经证明可以通过使用氨基酸作为促渗剂来调节胰岛素通过口腔粘膜的转运1。现在建议将这项工作扩展到研究使用涂覆有氨基酸的生物制剂的工程化复合微粒来帮助转运通过永生化的口腔细胞系1。据推测，这些包衣不仅可以保存生物活性，如实验室中使用其他功能性辅料所证明的那样，而且还可以调节通过颊粘膜的摄取。本课题的目的是研究氨基酸保护的复合微粒携带各种代表性生物制剂的口腔吸收。通过这种方式，将阐明调节一系列生物制剂的口腔转运所涉及的因素和机制，最终目的是为此类药物的更好制剂提供信息，并使这种非侵入性递送途径在未来生物制药药物中的使用更加自信。