The worldwide spread of antibiotic-resistant microorganisms can be viewed as an ecological consequence of the systematic use of antimicrobial agents. Resistant bacteria prevail in healthcare environments where antibiotic selective pressure is intensive. Novel therapeutic approaches are urgently required to deliver the well-documented existing drugs in an optimized fashion to: i) protect them toward degradation; ii) increase their bioavailability; iii) reduce toxic side effects; iv) increase patient compliance and iv) reduce treatment duration and related costs. In this sense, nanocarriers based on cyclodextrins (CDs) are particularly appealing for the delivery of antibiotics. This approach is of main interest for tuberculosis (TB), infections related to Salmonella Typhimurium, Staphyloccocus aureus and for species most frequently implicated in hospital infections such as enteric gram-negative rods. We will design and characterize CD-based nanocarriers, test their ability to encapsulate drugs, study their efficacy in vitro on bacteria and infected cells. The best formulation will be tested in vivo and scaled up. The objectives of the CycloN Hit project are to take full advantage of nanotechnology and of the high level interdisciplinary expertise of the partners to efficiently encapsulate and protect antibiotics in nanocarriers to combat resistant bacteria, and study the mechanisms in biological systems using state-of-the art techniques. This will be accomplished through a strong and demanding training program for 11 Early Stage and 5 young Experienced Researchers which will gather interdisciplinary expertise of 11 Full partners and 6 Associated partners, of which 7 are SMEs. Using the most recent advances in the nanomedicine field, the final goal of the CycloN Hit project is to bring to the preclinical studies an antibiotic formulation for the treatment of TB and more tailored alternative therapeutic approaches for other resistant microorganisms.