Developing a hollow fiber infection model system to determine the PK/PD of conjugated oligoelectrolytes against clinically relevant pathogens

The ability of microbes to develop antimicrobial resistance gives rise to the emergence of \ndrug resistant strains whose infections are difficult to treat. Therefore, there is a pressing need \nfor the development of novel drugs. One of the key stages in the drug discovery pipeline is \nunderstanding the pharmacokinetic/pharmacodynamic (PK/PD) of the new drug. The \nconventional in vitro methods for evaluating drug efficacy are often static and hence may not \ntruly reflect the in vivo conditions. Recently, hollow fiber bioreactors have emerged as a \nmodel system to mimic in vivo drug pharmacokinetics (PK) and pharmacodynamics (PD), \nwithout the need to access animal model experiments which requires specialized handling \nand are expensive to maintain. This is a useful technique that may accelerate the development \nof novel antimicrobial compounds such as the conjugated oligoelectrolytes (COEs). COEs are \na class of synthetic water-soluble molecules containing a conjugated core and pendant ionic \ngroups. COEs that are sufficiently shorter in molecular length as compared to the lipid bilayer \ninhibit microbial growth due to their membrane disrupting abilities. While COEs are \nemerging as potential low-cost antimicrobial agents, an understanding of the PK/PD of COEs \nis still required. Hence, this research would aim at developing the hollow fiber infection \nmodel (HFIM) system to determine the PK/PD of COEs against clinically relevant pathogens \nthat are often difficult to infect in conventional mouse models due to the intrinsic host \ndefense mechanisms.