Our Work

Biofilm-penetrating systems for novel therapeutic delivery

Many bacterial pathogens have evolved to adapt and survive in hostile environments such as pulmonary mucus and biofilms for Pseudomonas aeruginosa and MRSA infections. These environments are not only highly protective in terms of drug penetration, but the bacteria also enter a state of phenotypic antibiotic tolerance, greatly slowed metabolism, expression of drug efflux pumps, excretion of drug-degrading enzymes, and generation of biofilms that block penetration of small molecule drugs. The effect of such environments is to act as a route toward the generation of more resistant strains, while preventing response of the existing bacteria to treatment.

The goal of this project is to develop novel therapeutics that overcome these barriers. Specifically, we will generate novel layer-by-layer (LbL) nanoparticles designed to contain a range of water-soluble and insoluble drugs within a nanocarrier core surrounded by alternating charged layers of poly-cation and –anion that are selected for their ability to penetrate into and transport through biofilms. Attached to these nanoparticles will be novel therapeutics developed in the Dedon, Lu and Chan labs. Characterization of these systems will utilize models and methods developed at NTU in the Kline lab, and provide opportunities for further collaboration with additional members of the Singapore infectious disease community, including Kevin Pethe (LKCSM, NTU).