Respiratory diseases are the third leading cause of death worldwide. The translation of next-generation inhaled biological therapies into the clinic is hindered by a lack of laboratory tools – an area that experts (working groups of International Society for Aerosol Medicines and European Pharmaceutical Aerosol Group) have identified as a top research priority. The project will address this pressing unmet scientific need for innovative in vitro technology.
The student will develop research skills through the project, in which they will: a) learn the theory of aerosol science and apply it to the development of medical aerosols, and b) develop skills in establishing validated lung cell and tissue preparations to test the safety and efficacy of novel inhalable therapies.
The overarching aim of the project is to develop an assay platform for interfacing respirable aerosols with in vitro biological models of the respiratory tract. Specific objectives are:
FIRST YEAR.
Objective 1. Training in regulatory science. The student will be introduced to working groups and industry scientists collaborating on the development of assays and standards for inhaled biologics.
Objective 2. Produce a reference dataset for safety screening of inhaled drugs, excipients and formulations. This will be achieved by interfacing PreciseInhale aerosol delivery technology with precision-cut lung slices to establish a reference dataset.
Objective 3. Substitute more robust and scalable techniques for applying aerosols to more selective cell models. This will develop systems that are more amenable to implementation and validation as regulatory toxicology assays. This will be performed at Intertek and extend into year 2.
SECOND YEAR
Objective 4. Apply the platforms developed in year 1 to efficacy studies. Test formulations, e.g. nucleic acid formulations, will be varied systematically to possess different stability and efficacy profiles with which to establish test sensitivity.
THIRD YEAR
Objective 5. Extend studies to representative biopharmaceutical modalities from peptides, e.g. GLP-1 agonists, to less well characterised products, e.g. regenerative therapies based on extracellular vesicles.
Objective 6. Develop the cell/formulation interface for use with existing and emerging aerosol generating systems, e.g. electrospray or surface acoustic wave nebulisers, to produce a universal test system for testing biopharmaceuticals from the full spectrum of aerosol delivery devices.
FOURTH YEAR
The final year will enable problem-solving or validation of the assay platform as part of progress towards establishing recognised industry standards for biological aerosol medicine efficacy, safety and quality.