Use of materials made of cross-linked β-cyclodextrins for the treatment of tuberculosis

Abstract

Multi-drug resistant tuberculosis (TB) is a major public health problem concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10,000 tablets over a 2-year period. There is a clear need for efficient and better-formulated medications. The inventors have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, they report that in addition to be efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Indeed, empty pβCD are able to impair(Mtb) establishment after pulmonary administration in mice. pβCD hamper colonisation of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis leading to depletion of infected cells, thus creating a lung micro-environment detrimental to Mtb persistence. Taken together, the results suggest that materials made of cross-linked β-cyclodextrins (e.g. nanoparticles) loaded or not with antibiotics play an antibacterial action by its own and could be used as carrier in drug regimen formulations effective against TB.