Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against 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. We 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, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization 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 microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD 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.

Recent applications and strategies in nanotechnology for lung diseases

“…pβCD can prevent the colonization of macrophages by Mtb and does not produce toxicity in the body. In addition, pβCD can also induce macrophage apoptosis and promote the exhaustion of infected cells [157].…”

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

“…123 Some recent case studies of the CDs in the optimal drug delivery of drugs, proteins, peptides and aptamers are reported in the Table 3. [124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140] CDs can be moulded into various types of formulation for proving ease the drug delivery by diverse routes of administration.…”

A novel codrug made of the combination of ethionamide and its potentiating booster: synthesis, self-assembly into nanoparticles and antimycobacterial evaluation

“…This result demonstrated the benefit of using the pulmonary route of infection to target more specifically Mtb within reservoir cells. Using the same experimental design, we recently showed that ETH itself is ineffective when given intranasally in lungs during two weeks, 34 therefore a 6-fold reduction of the bacterial burden obtained after only 6 administrations of ETH-B NPs is encouraging. The next studies will aim at investigating whether an increase in the treatment duration or in the amount of administrated drugs could improve ETH-B efficacy.…”