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Project Topic
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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 are extremely difficult to treat due to the blood-brain barrier (BBB). There is, therefore, an urgent need to develop novel, non-antibiotic-based therapeutics, coupled with delivery systems for effective and targeted transport to the infection sites. This project aims to develop nanotechnology-based targeted drug delivery systems (nDDSs) to deliver novel, non-antibiotic, antibacterial agents and fight neuroinfectious 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 the BBB-crossing peptides. The so-obtained nanoformulations will be assessed for BBB crossing and antibacterial activity against neuroinfectious bacterial pathogens, in vitro, using cell-based experiments, and in vivo, using relevant animal models for bacterial meningitis. The most promising candidates will be identified for further preclinical studies. The success of this project will provide a proof-of-concept and a preclinical evidence for translating concepts into clinical studies against neuroinfectious bacterial pathogens. 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 generation of clinically relevant Intellectual Property, as well as a significant advance in antibacterial research and subsequent clinical application.
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