Projects per year
In the advent of the post-antibiotic era, new strategies are urgently required to improve the efficacy of antimicrobials and outsmart multi-drug resistant bacteria. Exploiting a basic survival mechanism of bacteria, lipase production, monoolein liquid crystal nanoparticles (MO-LCNPs) were investigated as a bacterial-triggered drug delivery system for three different antimicrobial compounds and compared with model sn-1/3 regiospecific and non-regiospecific lipases via pH-stat titration, proton nuclear magnetic resonance and in situ synchrotron small-angle X-ray scattering. The release of model hydrophobic (rifampicin) and macromolecular (alginate lyase) antimicrobials were triggered from MO-LCNPs at 82-fold and 7-fold higher rates (respectively) due to bacterial lipase digestion of MO-LCNPs, which could not be stimulated with a small hydrophilic antibiotic (ciprofloxacin HCl) or non-digestible, phytantriol-LCNPs. While sn-1/3 regiospecific lipase rapidly digested MO-LCNPs in a two-phase process, the single-phase digestion kinetics of the non-regiospecific lipase steadily digested the cubic Im3m structure and gave rise to lamellar structures that ultimately stimulated the triggered antibiotic release. Accordingly, MO-LCNPs have an application for localised Pseudomonas aeruginosa and Staphylococcus aureus infections that produce non-regiospecific lipases and for concentration-dependent antibiotics that have macromolecular (MW ~ 30 kDa) or hydrophobic (logP ~ 4) chemistries, as a triggered bolus release would be clinically efficacious for improved bacterial eradication.
- Liquid crystalline nanoparticles
- Triggered drug delivery
1/03/19 → 31/05/22
Davis, T., Boyd, B., Bunnett, N., Porter, C., Caruso, F., Kent, S., Thordarson, P., Kearnes, M., Gooding, J., Kavallaris, M., Thurecht, K., Whittaker, A., Parton, R., Corrie, S. R., Johnston, A., McGhee, J., Greguric, I. D., Stevens, M., Lewis, J., Lee, D. S., Alexander, C., Dawson, K., Hawker, C., Haddleton, D., Thierry, B., Prestidge, C. A., Meyer, A., Jones-Jayasinghe, N., Voelcker, N. H., Nann, T. & McLean, K.
Australian Research Council (ARC), Monash University, University of Melbourne, University of New South Wales, University of Queensland , University of South Australia, Monash University – Internal Faculty Contribution, University of Wisconsin-Madison, Memorial Sloan Kettering Cancer Center, University of California System, University College Dublin, Imperial College London, University of Warwick, SungKyunKwan University, Australian Nuclear Science and Technology Organisation (ANSTO) , University of Nottingham
30/06/14 → 29/06/21