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

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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.