NAREB · Nanotherapeutics for antibiotic resistant emerging bacterial pathogens

Increase in antibiotic resistance is a global concern worldwide. The project NAREB's main objective is the optimization of several nanoformulations of antibacterial therapeutics in order to improve the therapy of multi-drug resistant (MDR) tuberculosis (TB) and MRSA infections in European MDR patients.NAREB will address the problem of drug bioavailability inside the infected macrophages, transport across the bacterial cell wall, and avoidance of escape mechanisms (expressed by the pathogen). The success of the utilization of nanoparticles in the improvement of drug targeting in other diseases opens the way for novel applications in nanotechnology-based treatments aimed at controlling MDR-TB and MRSA.Specific objectives to achieve the main goal are:(i) Screening of different combinations of antibiotic drugs (small chemical molecules and/or biomacromolecules - glycopeptides) with nanocarriers (lipid, polymeric, biopolymeric);(ii) Loading of Transcription Factor Decoys (TFDs) designed to block the expression of essential bacterial genes in compatible nanoparticle systems and their testing as novel antibacterials;(iii) In vitro and in vivo testing of the best therapeutic combinations in relevant experimental models and using innovative bioimaging;(iv) Improved formulations of multifunctional particles containing selected antibiotics and TFDs for increasing the bioavailability of active molecules in the site of infection (targeting strategy, adapted route of administration)(v) Assessing safety, regulatory and production (GLP/GMP) aspects in relation with the most promising nanoformulations;(vi) Clinical Development Plan for the preparatory work for the subsequent clinical testing of the selected nanoformulations.The project NAREB brings together 15 partners (including 4 SMEs and 1 industry) from 8 EU Member and Associated States with outstanding complementary expertise, ranging from material engineering to molecular biology, pharmacology and medicine.