Supramolecular peptide nanotechnology for antimicrobial therapies (360G-Wellcome-210122_Z_18_Z)

Antimicrobials remain the main means to treat and control bacterial infections, but their efficacy is now compromised due to overuse in humans, animals, agriculture, with bacteria developing resistance that renders certain antibiotics ineffective. Infections due multi-drug resistant (MDR) bacteria have emerged as one of the most significant global threats to human and animal health in the 21st century. Thus, the development of new antibiotics, or better ways to deliver existing antibiotics more effectively, is an urgent priority. Polymyxins are "old" antibiotics that have re-emerged as the last resort for treating infections caused by MDR Gram-negative bacteria. There are two polymyxins in clinical use, polymyxin B and polymyxin E (colistin), but their low stability, unpredictable pharmacokinetics and nephrotoxicity still raise significant concerns. We hypothesize that nano-engineered carriers will be able to restore and/or enhance the efficacy of polymyxins against MDR Gram-negative bacteria by improving their pharmacokinetic profiles, compared to standard mono and dual antimicrobial formulations, whilst minimizing the risks of adverse systemic effects. We will develop and optimize novel self-assembled nanocarriers for the controlled delivery of polymyxins and assess their potential to treat more effectively bacterial-related infections. This data will make the basis for future grant applications under the AMR initiatives.