Dataset Information

Intrinsic Antibacterial Activity of Nanoparticles Made of ?-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-?-cyclodextrins (p?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?CD nanoparticles are endowed with intrinsic antibacterial properties. Empty p?CD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. p?CD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, p?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?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.

SUBMITTER: Machelart A

PROVIDER: S-EPMC6718168 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Machelart Arnaud A Salzano Giuseppina G Li Xue X Demars Aurore A Debrie Anne-Sophie AS Menendez-Miranda Mario M Pancani Elisabetta E Jouny Samuel S Hoffmann Eik E Deboosere Nathalie N Belhaouane Imène I Rouanet Carine C Simar Sophie S Talahari Smaïl S Giannini Valerie V Villemagne Baptiste B Flipo Marion M Brosch Roland R Nesslany Fabrice F Deprez Benoit B Muraille Eric E Locht Camille C Baulard Alain R AR Willand Nicolas N Majlessi Laleh L Gref Ruxandra R Brodin Priscille P

ACS nano 20190308 4

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 ...[more]

PMID: 30822386

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Project description:Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN-glycerol monostearate, GM, as the lipid and ATO5-SLNs-glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of electroporation improved the transport of encapsulated and free C6 into both treated cell lines.

Dataset Information

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

Publications

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

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