SANS study of lipid-based nanocarriers as inhaled drug delivery systems for anti-tuberculosis chemotherapy

Tuberculosis (TB) remains one of the world’s deadliest communicable diseases. In pulmonary infections Mycobacterium tuberculosis (Mtb) multiplies within alveolar macrophages that are difficult to be reached by the most part of antibiotics. Inhalation therapy is a promising alternative to conventional treatments, as it allows the release of the drug directly at the infection site avoiding the serious side effects in other districts and the drug resistance phenomenon. Recently, new drug delivery carriers based on liposomes and solid lipid nanoparticles (SLN) have been proposed [1] in the inhaled therapy to improve the drug targeting and delivery. Here, we report on our deeper structural understanding of drugs (isoniazid and rifampicin) distribution within these nanocarriers, by means of SANS, which is a key knowledge for defining the encapsulation efficacy and stability of these drugs into nanoparticles, that strongly affects their antitubercular potentiality. These outcomes will be useful also for conceiving further loading experiments of our recently identified competitive MbtI inhibitors, exhibiting a promising antibiotic activity, and their co-loading with isoniazid or rifampicin in the same nanoparticle, for allowing a synergistic action after their local lung administration.