Project No. 2306
Dr Stefano Biagini – University of Kent
Dr Christopher Serpell- University of Kent
Dr Garry Robinson- University of Kent
Dr Darren Pitt- VisuNano Ltd (CASE Partner)
Project Aim: Isolate and develop murein succuli as drug delivery systems.
Drug delivery systems are an essential component of precision medicine and are increasingly required for the development of both new drugs and modified old drugs. Drug delivery vehicles should ideally be non-toxic, biocompatible and biodegradable and capable of being safely excreted by the body. They should have controllable drug-release profiles and reliable and reproducible preparation.
Gram-negative bacterial cells are encased by the murein succulus, which is a macromolecular sac enveloping the cytoplasmic membrane and is essential for protection of the cell from rupture caused by internal pressure. Chemically, the murein succulus is a three-dimensional peptidoglycan biopolymer whereby alternating β1,4-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) residues are cross-linked by short peptides. It is possible to isolate murein succulus intact from bacterial cells, and this has been done to study their physical properties. It is also known that the murein succulus is porous to a range of chemicals and this therefore offers the opportunity to investigate these structures as drug delivery vehicles, both from a simple slow-diffusion of drug model, or as a carrier that can be degraded by in situ lysozymes (e.g. as found in eye fluids). The sacculi (and fragments thereof) are invariably likely to be immunogenic, however as seen with genetically engineered bacteria the immune response can become part of the delivery process. Unlike live organism however sacculi do not present with the dangers of bacterial viability. We will also investigate chemical modifications of the sacculi (e.g. acetylation, PEGylation) such as to alter its physicochemical and biological parameters. These models will be evaluated under in vitro conditions, and within a cutting-edge synthetic whole-eye model.
The project would suit candidates with a background in chemistry and some biological knowledge.