Abstract:

Antibiotic resistance is a growing health crisis worldwide. The indiscriminate overuse of antibiotics to treat bacterial infections, led to the emergence of drug-resistant bacteria, which incurs a substantial healthcare and financial burden globally. In particular, bacterial infections affecting the center nervous system (CNS) are extremely difficult to treat due to the blood-brain barrier (BBB). Therefore, there is an urgent need for novel and non-antibiotic-based therapeutics coupled with delivery systems for effective and targeted transport to the infection sites in brain.

This project aims to develop nanotechnology-based targeted drug delivery systems (nDDSs) to deliver innovative antibacterial agents and fight neuroinvasive bacterial pathogens, using bacterial meningitis as a proof-of-concept study. Specifically, novel and stable antimicrobial peptides (AMPs), with potent antibiotic activity, will be designed, synthetized and evaluated as non-antibiotic agents. Promising AMPs will be encapsulated within lipid-, polymer- and dendrimer-based nDSSs, which will then be decorated with BBB-homing peptides. The so-obtained nanoformulations will be assessed for BBB crossing and antibacterial activity against neuroinvasive bacterial pathogens in vitro, using cell-based experiments, and in vivo using relevant animal models for bacterial meningitis.

The most promising candidates will be used for further preclinical studies. The success of this project will provide a proof-of-concept and preclinical evidence for translating concepts into clinical studies against bacterial neuropathogens. We expect to establish an effective nanomedical strategy for downstream investigational new drug-enabling preclinical, scale-up, and regulatory studies.

The project is highly likely to result in the generation of clinically relevant Intellectual Property, as well as significant advances in antibacterial research and subsequent clinical applications.