Intrinsic Antibacterial Activity of Nanoparticles Made of beta-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis

摘要

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. We have previously shown that nanoparticles made of cross-linked poly-beta-cyclodextrins (p beta CD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, p beta CD nanoparticles are endowed with intrinsic antibacterial properties. Empty p beta CD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. p beta CD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, p beta CD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that p beta CD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB.