Callum Hay

Developing artificial cells for delivering drug molecules to micro-engineered heart tissue

Callum Hay - MRes


Current therapies for acute myocardial infarction restore oxygenated blood flow to the heart muscle, but none acts directly to suppress cell death itself. One recognized limitation is the lack of drug delivery systems specific for the damaged tissue, as needed to minimize potential confounding on- and off-target effects. Surface-modified liposomes provide an auspicious means to achieve targeted delivery, provided that suitable ligands are identified. Intriguingly microfluidic fabrication of liposomes has recently been achieved offering precise control of size, cargo and membrane contents. This technology has the potential to be adapted to manufacture multi-lamellar liposomes (babushkasomes) where each layer of the delivery vehicle can be fine-tuned to accommodate different targetting vectors and a series of user defined drug payloads that are released one at a time depending on the architecture of the liposomes (multi-drug targeting with spatio-temporal control). The cargo within each layer could instead be the same leading to extended multi-stage drug release profiles. We intend to exploit the recent discovery of peptides specific to cardiomyocytes and endothelial cells by coupling them to the babushkasome technology leading to a new generation of target specific liposomes for delivering small molecules to the border zone of the remodelling infarct. The efficacy of this platform will be validated by manufacturing organ-on-a-chip technologies coupled with single cell readout that enable us to assess the efficacy of both the delivery vehicles and their drug payloads. This will lead to an integrated platform for both drug discovery and target specific release.