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Localised antibiotic delivery and release with luminescent mesoporous silica nanoparticles

Principal Supervisor: Professor Zoe Pikramenou, School of Chemistry

Co-supervisor: Dr Jessica Blair, Institute of Microbiology and Infection

PhD project title: Localised antibiotic delivery and release with luminescent mesoporous silica nanoparticles

University of Registration: University of Birmingham

Project outline:

Background

Bacterial infections are becoming harder to treat as antibiotic resistance becomes increasingly prevalent. There is also a lack of drugs in the pipeline to take the place of those that can no longer be used due to resistance and novel therapeutic options are needed.

Many Gram-negative pathogens, such as Pseudomonas aeruginosa, are particularly difficult to treat because their membrane structure makes them relatively impermeable to many antibiotics. This project will develop a novel tool using silica nanoparticles to deliver antibiotic molecules across the membranes of these bacteria. This novel drug delivery system will increase efficacy of antibiotic treatment and provide new treatment options for hard to treat infections, particularly those that cause wound or surface infections.

Mesoporous silica nanoparticles (MSN) can act as efficient tools for drug delivery as morphologies with high surface area of more than 900 m2/g and pore volume over 0.9 cm3/g both of which ensure sufficient loading of drugs. The sizes of the MSNs are usually 100-300 nm in diameter and pores can be designed to be hexagonal of about 4 nm to include drug molecules. However, one of the disadvantages is the loading of the drug to the silica nanoparticles which include unspecific binding of the drug to the surface of the silica and consequently fast release of the drug (Figure 1,).

 

 image1

Figure 1. MSN with loaded drug and MSN with pre-included drug.

Objectives In this project we will develop MSN using a method to allow preinclusion of drug in the silica structure together with a luminescent metal centre (such as ruthenium, iridium complexes). Release of the drug will be controlled with ultrasound or photoactivation to allow localized delivery of the MSN.

 References:

  • Santos, A, Aw, M.S., Bariana, M., Kumeria, T., Wang, Y., Losic ,D. J Mater Chem B., 2014, 2, 6157–6182.
  • Lewis, D., Dore, V., Rogers, N., Mole, T., Nash, G., Angeli, P. and Pikramenou, Z. Langmuir, 2013, 29, 14701.

BBSRC Strategic Research Priority: Molecules, Cells and Systems

Techniques that will be undertaken during the project:

  • Material and molecular synthesis
  • Characterization with DLS and electron microscopy
  • Metal complex preparation
  • Spectroscopies to monitor drug loading,

The project will involve training in basic microbiology and antimicrobial susceptibility testing. We will also develop assays to assess how likely it is that the bacteria will develop resistance to this type of treatment.

Contact: Professor Zoe Pikramenou, School of Chemistry