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

Autor:	Machelart A; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Salzano G; Université Paris Sud, Université Paris-Saclay , CNRS, UMR 8214 - Institute for Molecular Sciences of Orsay (ISMO) , F-91405 Orsay , France., Li X; Université Paris Sud, Université Paris-Saclay , CNRS, UMR 8214 - Institute for Molecular Sciences of Orsay (ISMO) , F-91405 Orsay , France., Demars A; Research Unit in Microorganisms Biology (URBM), Laboratory of Immunology and Microbiology , Université de Namur , Narilis , B-5000 Namur , Belgium., Debrie AS; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Menendez-Miranda M; Université Paris Sud, Université Paris-Saclay , CNRS, UMR 8214 - Institute for Molecular Sciences of Orsay (ISMO) , F-91405 Orsay , France., Pancani E; Université Paris Sud, Université Paris-Saclay , CNRS, UMR 8214 - Institute for Molecular Sciences of Orsay (ISMO) , F-91405 Orsay , France., Jouny S; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Hoffmann E; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Deboosere N; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Belhaouane I; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Rouanet C; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Simar S; Université de Lille , Institut Pasteur de Lille , EA 4483, F-59000 Lille , France., Talahari S; Université de Lille , Institut Pasteur de Lille , EA 4483, F-59000 Lille , France., Giannini V; Institut Pasteur , Unit for Integrated Mycobacterial Pathogenomics, Paris , CNRS UMR 3525, 25 Rue du Dr. Roux , F-75015 Paris , France., Villemagne B; Université de Lille , INSERM, Institut Pasteur de Lille , U1177 - Drugs and Molecules for living Systems, F-59000 Lille , France., Flipo M; Université de Lille , INSERM, Institut Pasteur de Lille , U1177 - Drugs and Molecules for living Systems, F-59000 Lille , France., Brosch R; Institut Pasteur , Unit for Integrated Mycobacterial Pathogenomics, Paris , CNRS UMR 3525, 25 Rue du Dr. Roux , F-75015 Paris , France., Nesslany F; Université de Lille , Institut Pasteur de Lille , EA 4483, F-59000 Lille , France., Deprez B; Université de Lille , INSERM, Institut Pasteur de Lille , U1177 - Drugs and Molecules for living Systems, F-59000 Lille , France., Muraille E; Research Unit in Microorganisms Biology (URBM), Laboratory of Immunology and Microbiology , Université de Namur , Narilis , B-5000 Namur , Belgium.; Laboratory of Parasitology, Faculty of Medicine , Université Libre de Bruxelles , B-1070 Brussels , Belgium., Locht C; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Baulard AR; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France., Willand N; Université de Lille , INSERM, Institut Pasteur de Lille , U1177 - Drugs and Molecules for living Systems, F-59000 Lille , France., Majlessi L; Institut Pasteur , Unit for Integrated Mycobacterial Pathogenomics, Paris , CNRS UMR 3525, 25 Rue du Dr. Roux , F-75015 Paris , France., Gref R; Université Paris Sud, Université Paris-Saclay , CNRS, UMR 8214 - Institute for Molecular Sciences of Orsay (ISMO) , F-91405 Orsay , France., Brodin P; Université de Lille , CNRS, INSERM, CHU Lille, Institut Pasteur de Lille , U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille , France.
Jazyk:	angličtina
Zdroj:	ACS nano [ACS Nano] 2019 Apr 23; Vol. 13 (4), pp. 3992-4007. Date of Electronic Publication: 2019 Mar 08.
DOI:	10.1021/acsnano.8b07902
Abstrakt:	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.
Databáze:	MEDLINE
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