In the last years, the increase in antimicrobial resistance, together with a lack of new drugs for the treatment of bacterial infections resistant to classical antibiotics are of growing concern. Moreover, some of current therapies induce severe side effects and are often difficult to administer. In 2012 the FDA approved the use of bedaquiline, as the first new very effective drug against TB in the last 40 years. Despite its effectiveness, unfortunately bedaquiline side effects can be so dangerous that at present it is to be prescribed only when no other treatment options are available. The development of effective and safe nanotechnology-based methods can be particularly relevant to increase antimicrobial concentration at the site of infection, to reduce doses in the general circulation, which in turn reduces adverse effects. In this work bedaquiline was encapsulated in two types of nanocarriers, lipid nanoparticles and chitosan-based nanocapsules with high encapsulation efficiency and drug loading values. The efficacy of the drug-encapsulating nanocarriers has been demonstrated in vitro against Mycobacterium tuberculosis, together with the excellent compatibility of both carriers with animal cells. The obtained results open the way for further studies on multi-drug resistant strains of M. tuberculosis and for in vivo studies of the optimized nanocarriers. The promising behaviour of drug-loaded nanocarriers will hopefully lead

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The tunability of the properties of chitosan-based carriers opens new ways for the application of drugs with low water-stability or high adverse effects. In this work, the combination of a nanoemulsion with a chitosan hydrogel coating and the following poly (ethylene glycol) (PEG) grafting is proven to be a promising strategy to obtain a flexible and versatile nanocarrier with an improved stability. Thanks to chitosan amino groups, a new easy and reproducible method to obtain nanocapsule grafting with PEG has been developed in this work, allowing a very good control and tunability of the properties of nanocapsule surface. Two different PEG densities of coverage are studied and the nanocapsule systems obtained are characterized at all steps of the optimization in terms of diameter, Z potential and surface charge (amino group analysis). Results obtained are compatible with a conformation of PEG molecules laying adsorbed on nanoparticle surface after covalent linking through their amino terminal moiety. An improvement in nanocapsule stability in physiological medium is observed with the highest PEG coverage density obtained. Cytotoxicity tests also demonstrate that grafting with PEG is an effective strategy to modulate the cytotoxicity of developed nanocapsules. Such results indicate the suitability of chitosan as protective coating for future studies oriented toward drug delivery.