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

第一年结束时确认：MIBTP学生在第一年接受一段时间的培训。这包括统计学、编程、数据分析、人工智能和小型研究项目等必修教学模块。项目确认：生物制剂，如蛋白质和多肽，具有巨大的治疗潜力，自1982年首次批准重组胰岛素以来，许多蛋白质正在开发用于临床应用。虽然非侵入性给药途径是首选，但对于大多数治疗性蛋白质，肠外给药仍然是主要的给药途径，例如糖尿病患者使用皮下胰岛素。很少有治疗性蛋白质通过口服途径进入III期临床试验，因为它的环境不友好，专为营养物质的分解代谢而设计，与生物制剂的物理化学性质完全不相容，这些特性反过来又造成了从消化道到体循环的运输困难。出于这个原因，阿斯顿的研究主要集中在生物制剂的口腔给药上，最近有研究表明，胰岛素在口腔黏膜的转运可以通过使用氨基酸作为佐剂来调节。现在有人建议将这项工作扩展到研究使用氨基酸包被的生物制品的工程复合微颗粒来协助通过永生化口腔细胞系的运输1。据推测，这些涂层不仅可以保持生物活性，正如实验室中与其他功能性赋形剂一起证明的那样，而且还可以调节口腔黏膜的吸收。本课题旨在研究氨基酸保护复合颗粒携带多种代表性生物制剂的口腔吸收。通过这种方式，参与调节一系列生物制剂口腔运输的因素和机制将被阐明，最终目的是为这些制剂的更好配方提供信息，并使这种非侵入性给药途径在未来的生物制药药物中得到更有信心的使用。

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.