Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis

Arnaud Machelart, Giuseppina Salzano, Xue Li, Aurore Demars, Anne Sophie Debrie, Mario Menendez-Miranda, Elisabetta Pancani, Samuel Jouny, Eik Hoffmann, Nathalie Deboosere, Imène Belhaouane, Carine Rouanet, Sophie Simar, Smaïl Talahari, Valerie Giannini, Baptiste Villemagne, Marion Flipo, Roland Brosch, Fabrice Nesslany, Benoit DeprezEric Muraille, Camille Locht, Alain R. Baulard, Nicolas Willand, Laleh Majlessi, Ruxandra Gref, Priscille Brodin

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3992-4007
Number of pages16
JournalACS nano
Volume13
Issue number4
DOIs
Publication statusPublished - 23 Apr 2019

Fingerprint

tuberculosis
Cyclodextrins
drugs
Nanoparticles
nanoparticles
Pharmaceutical Preparations
macrophages
Macrophages
rafts
public health
Drug Carriers
tablets
antibiotics
apoptosis
Public health
Antibiotics
Cell death
Medical problems
toxicity
lungs

Keywords

  • antibacterial activity
  • cyclodextrins
  • drug nanocarrier
  • host-directed therapy
  • tuberculosis

Cite this

Machelart, Arnaud ; Salzano, Giuseppina ; Li, Xue ; Demars, Aurore ; Debrie, Anne Sophie ; Menendez-Miranda, Mario ; Pancani, Elisabetta ; Jouny, Samuel ; Hoffmann, Eik ; Deboosere, Nathalie ; Belhaouane, Imène ; Rouanet, Carine ; Simar, Sophie ; Talahari, Smaïl ; Giannini, Valerie ; Villemagne, Baptiste ; Flipo, Marion ; Brosch, Roland ; Nesslany, Fabrice ; Deprez, Benoit ; Muraille, Eric ; Locht, Camille ; Baulard, Alain R. ; Willand, Nicolas ; Majlessi, Laleh ; Gref, Ruxandra ; Brodin, Priscille. / Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis. In: ACS nano. 2019 ; Vol. 13, No. 4. pp. 3992-4007.
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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.",
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Machelart, A, Salzano, G, Li, X, Demars, A, Debrie, AS, Menendez-Miranda, M, Pancani, E, Jouny, S, Hoffmann, E, Deboosere, N, Belhaouane, I, Rouanet, C, Simar, S, Talahari, S, Giannini, V, Villemagne, B, Flipo, M, Brosch, R, Nesslany, F, Deprez, B, Muraille, E, Locht, C, Baulard, AR, Willand, N, Majlessi, L, Gref, R & Brodin, P 2019, 'Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis', ACS nano, vol. 13, no. 4, pp. 3992-4007. https://doi.org/10.1021/acsnano.8b07902

Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis. / Machelart, Arnaud; Salzano, Giuseppina; Li, Xue; Demars, Aurore; Debrie, Anne Sophie; Menendez-Miranda, Mario; Pancani, Elisabetta; Jouny, Samuel; Hoffmann, Eik; Deboosere, Nathalie; Belhaouane, Imène; Rouanet, Carine; Simar, Sophie; Talahari, Smaïl; Giannini, Valerie; Villemagne, Baptiste; Flipo, Marion; Brosch, Roland; Nesslany, Fabrice; Deprez, Benoit; Muraille, Eric; Locht, Camille; Baulard, Alain R.; Willand, Nicolas; Majlessi, Laleh; Gref, Ruxandra; Brodin, Priscille.

In: ACS nano, Vol. 13, No. 4, 23.04.2019, p. 3992-4007.

Research output: Contribution to journalArticle

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AU - Machelart, Arnaud

AU - Salzano, Giuseppina

AU - Li, Xue

AU - Demars, Aurore

AU - Debrie, Anne Sophie

AU - Menendez-Miranda, Mario

AU - Pancani, Elisabetta

AU - Jouny, Samuel

AU - Hoffmann, Eik

AU - Deboosere, Nathalie

AU - Belhaouane, Imène

AU - Rouanet, Carine

AU - Simar, Sophie

AU - Talahari, Smaïl

AU - Giannini, Valerie

AU - Villemagne, Baptiste

AU - Flipo, Marion

AU - Brosch, Roland

AU - Nesslany, Fabrice

AU - Deprez, Benoit

AU - Muraille, Eric

AU - Locht, Camille

AU - Baulard, Alain R.

AU - Willand, Nicolas

AU - Majlessi, Laleh

AU - Gref, Ruxandra

AU - Brodin, Priscille

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N2 - 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.

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KW - cyclodextrins

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