Label-free Imaging for Studying Drug Delivery across Biophysical Barriers

Drug delivery platforms are needed to target therapy to required locations and to improve its efficacy. However, key to developing and optimising such drug delivery vehicles is the ability to monitor, visualise and evaluate them on their performance across the biophysical barriers existing in vivo such as cell and organelle membranes, the blood-brain barrier and other specialised uptake and efflux mechanisms. Non-ionic surfactant vesicles (NISVs) are a promising platform technology that can be used to deliver a variety of drugs (both hydrophilic and hydrophobic) including anti-microbials. However, the tools for their evaluation both at the cell and the tissue level do not exist. Questions such as whether they remain intact on translocation across cells, their intracellular/tissue fate or the amount of drug deposited by them remain unanswered. Label-free techniques such as those based on Raman spectroscopy such as coherent Raman imaging and non-linear techniques including second harmonic imaging offer a non-invasive and non-destructive way of characterising and imaging NISVs and their therapeutic payload. In this project these approaches for intracellular and tissue imaging will be developed to answer questions exploring NISVs as viable drug delivery systems. Any success with achieving these goals will have wide-ranging impact as it will additionally be useful in development of drugs, drug delivery platforms and the treatment of infectious diseases as well as understanding pharmacological performance, for example, by the sensitive detection of other widely-used chemicals with essential therapeutic effects e.g. insulin, corticosteroids, synthetic hormones, chemotherapies.