Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis

Dulce Mata-Espinosa, Gloria María Molina-Salinas, Jorge Barrios-Payán, Gabriel Navarrete-Vázquez, Brenda Marquina, Octavio Ramos-Espinosa, Estela Isabel Bini, Isabel Baeza, Rogelio Hernández-Pando

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Abstract

© 2015 Elsevier Ltd. Background and objectives: Tuberculosis (TB) is one of the deadliest infectious diseases and comprises a global public health concern because co-infection with Human immunodeficiency virus (HIV) and, in particular, the continuous isolation of new Multidrug-resistant strains (MDR), rendering the discovery of novel anti-TB agents a strategic priority. One of the most effective first-line mycobactericidal drugs is Isoniazid (INH). Previously, we reported in vitro anti-mycobacterial activity against sensitive and MDR Mycobacterium tuberculosis strains of a new oxadiazole obtained from the hybridization of INH and palmitic acid. The present study evaluated the therapeutic potential of liposomes including Phosphatidylcholine (PC) and L-α Phosphatidic acid (PA) or PC and Cholesterol (Chol) containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in BALB/c male mice infected by intratracheal (i.t.) route with drug-sensitive or MDR M. tuberculosis. Methods: The lipophilic 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine was obtained to mix INH and palmitoyl chloride. The in vivo anti-TB effect of this oxadiazole derivative contained in two different liposomes was tested in BALB/c mice infected with a sensitive strain of M. tuberculosis, initiating treatment 2 months post-infection, by i.t. route, of 50 μg of oxadiazole derivative for 1 month. In a second stage, mice were infected with an MDR (resistant to first-line drugs) and treated with 150 μg of an oxadiazole derivative carried by PC + Chol liposomes for 2 months. The effect of the oxadiazole derivative in vivo was determined by the quantification of lung bacilli loads and histopathology. Results: In comparison with control animals, drug-sensitive, strain-infected mice treated for 1 month with 50 μg of this oxadiazole derivative contained in the liposomes of PC + Chol showed a significant, 80% decrease of live bacilli in lungs, which correlated with the morphometric observation, and the group of MDR clinical isolate-infected mice treated with 150 μg of the oxadiazole derivative contained in the same type of liposome showed significantly lower lung bacillary loads than control mice, producing 90% of bacilli burden reduction after 2 months of treatment. Conclusion: These results confirm and extend the reported highly efficient anti-mycobacterial activity of this lipophilic oxidazole derivative when it is carried by liposomes in mice suffering from late progressive pulmonary TB induced by drug-sensitive, and most prominently by, MDR strains.
Original languageAmerican English
Pages (from-to)7-14
Number of pages5
JournalPulmonary Pharmacology and Therapeutics
DOIs
StatePublished - 1 Jan 2015

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Oxadiazoles
Pulmonary Tuberculosis
Liposomes
Derivatives
Phosphatidylcholines
Bacilli
Mycobacterium tuberculosis
Bacillus
Tuberculosis
Pharmaceutical Preparations
Cholesterol
Lung
Therapeutics
Phosphatidic Acids
Palmitic Acid
Drug and Narcotic Control
Isoniazid
Public health
4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine
pyridine

Cite this

Mata-Espinosa, D., Molina-Salinas, G. M., Barrios-Payán, J., Navarrete-Vázquez, G., Marquina, B., Ramos-Espinosa, O., ... Hernández-Pando, R. (2015). Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis. Pulmonary Pharmacology and Therapeutics, 7-14. https://doi.org/10.1016/j.pupt.2015.03.004
Mata-Espinosa, Dulce ; Molina-Salinas, Gloria María ; Barrios-Payán, Jorge ; Navarrete-Vázquez, Gabriel ; Marquina, Brenda ; Ramos-Espinosa, Octavio ; Bini, Estela Isabel ; Baeza, Isabel ; Hernández-Pando, Rogelio. / Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis. In: Pulmonary Pharmacology and Therapeutics. 2015 ; pp. 7-14.
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title = "Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis",
abstract = "{\circledC} 2015 Elsevier Ltd. Background and objectives: Tuberculosis (TB) is one of the deadliest infectious diseases and comprises a global public health concern because co-infection with Human immunodeficiency virus (HIV) and, in particular, the continuous isolation of new Multidrug-resistant strains (MDR), rendering the discovery of novel anti-TB agents a strategic priority. One of the most effective first-line mycobactericidal drugs is Isoniazid (INH). Previously, we reported in vitro anti-mycobacterial activity against sensitive and MDR Mycobacterium tuberculosis strains of a new oxadiazole obtained from the hybridization of INH and palmitic acid. The present study evaluated the therapeutic potential of liposomes including Phosphatidylcholine (PC) and L-α Phosphatidic acid (PA) or PC and Cholesterol (Chol) containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in BALB/c male mice infected by intratracheal (i.t.) route with drug-sensitive or MDR M. tuberculosis. Methods: The lipophilic 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine was obtained to mix INH and palmitoyl chloride. The in vivo anti-TB effect of this oxadiazole derivative contained in two different liposomes was tested in BALB/c mice infected with a sensitive strain of M. tuberculosis, initiating treatment 2 months post-infection, by i.t. route, of 50 μg of oxadiazole derivative for 1 month. In a second stage, mice were infected with an MDR (resistant to first-line drugs) and treated with 150 μg of an oxadiazole derivative carried by PC + Chol liposomes for 2 months. The effect of the oxadiazole derivative in vivo was determined by the quantification of lung bacilli loads and histopathology. Results: In comparison with control animals, drug-sensitive, strain-infected mice treated for 1 month with 50 μg of this oxadiazole derivative contained in the liposomes of PC + Chol showed a significant, 80{\%} decrease of live bacilli in lungs, which correlated with the morphometric observation, and the group of MDR clinical isolate-infected mice treated with 150 μg of the oxadiazole derivative contained in the same type of liposome showed significantly lower lung bacillary loads than control mice, producing 90{\%} of bacilli burden reduction after 2 months of treatment. Conclusion: These results confirm and extend the reported highly efficient anti-mycobacterial activity of this lipophilic oxidazole derivative when it is carried by liposomes in mice suffering from late progressive pulmonary TB induced by drug-sensitive, and most prominently by, MDR strains.",
author = "Dulce Mata-Espinosa and Molina-Salinas, {Gloria Mar{\'i}a} and Jorge Barrios-Pay{\'a}n and Gabriel Navarrete-V{\'a}zquez and Brenda Marquina and Octavio Ramos-Espinosa and Bini, {Estela Isabel} and Isabel Baeza and Rogelio Hern{\'a}ndez-Pando",
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language = "American English",
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Mata-Espinosa, D, Molina-Salinas, GM, Barrios-Payán, J, Navarrete-Vázquez, G, Marquina, B, Ramos-Espinosa, O, Bini, EI, Baeza, I & Hernández-Pando, R 2015, 'Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis', Pulmonary Pharmacology and Therapeutics, pp. 7-14. https://doi.org/10.1016/j.pupt.2015.03.004

Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis. / Mata-Espinosa, Dulce; Molina-Salinas, Gloria María; Barrios-Payán, Jorge; Navarrete-Vázquez, Gabriel; Marquina, Brenda; Ramos-Espinosa, Octavio; Bini, Estela Isabel; Baeza, Isabel; Hernández-Pando, Rogelio.

In: Pulmonary Pharmacology and Therapeutics, 01.01.2015, p. 7-14.

Research output: Contribution to journalArticle

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T1 - Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis

AU - Mata-Espinosa, Dulce

AU - Molina-Salinas, Gloria María

AU - Barrios-Payán, Jorge

AU - Navarrete-Vázquez, Gabriel

AU - Marquina, Brenda

AU - Ramos-Espinosa, Octavio

AU - Bini, Estela Isabel

AU - Baeza, Isabel

AU - Hernández-Pando, Rogelio

PY - 2015/1/1

Y1 - 2015/1/1

N2 - © 2015 Elsevier Ltd. Background and objectives: Tuberculosis (TB) is one of the deadliest infectious diseases and comprises a global public health concern because co-infection with Human immunodeficiency virus (HIV) and, in particular, the continuous isolation of new Multidrug-resistant strains (MDR), rendering the discovery of novel anti-TB agents a strategic priority. One of the most effective first-line mycobactericidal drugs is Isoniazid (INH). Previously, we reported in vitro anti-mycobacterial activity against sensitive and MDR Mycobacterium tuberculosis strains of a new oxadiazole obtained from the hybridization of INH and palmitic acid. The present study evaluated the therapeutic potential of liposomes including Phosphatidylcholine (PC) and L-α Phosphatidic acid (PA) or PC and Cholesterol (Chol) containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in BALB/c male mice infected by intratracheal (i.t.) route with drug-sensitive or MDR M. tuberculosis. Methods: The lipophilic 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine was obtained to mix INH and palmitoyl chloride. The in vivo anti-TB effect of this oxadiazole derivative contained in two different liposomes was tested in BALB/c mice infected with a sensitive strain of M. tuberculosis, initiating treatment 2 months post-infection, by i.t. route, of 50 μg of oxadiazole derivative for 1 month. In a second stage, mice were infected with an MDR (resistant to first-line drugs) and treated with 150 μg of an oxadiazole derivative carried by PC + Chol liposomes for 2 months. The effect of the oxadiazole derivative in vivo was determined by the quantification of lung bacilli loads and histopathology. Results: In comparison with control animals, drug-sensitive, strain-infected mice treated for 1 month with 50 μg of this oxadiazole derivative contained in the liposomes of PC + Chol showed a significant, 80% decrease of live bacilli in lungs, which correlated with the morphometric observation, and the group of MDR clinical isolate-infected mice treated with 150 μg of the oxadiazole derivative contained in the same type of liposome showed significantly lower lung bacillary loads than control mice, producing 90% of bacilli burden reduction after 2 months of treatment. Conclusion: These results confirm and extend the reported highly efficient anti-mycobacterial activity of this lipophilic oxidazole derivative when it is carried by liposomes in mice suffering from late progressive pulmonary TB induced by drug-sensitive, and most prominently by, MDR strains.

AB - © 2015 Elsevier Ltd. Background and objectives: Tuberculosis (TB) is one of the deadliest infectious diseases and comprises a global public health concern because co-infection with Human immunodeficiency virus (HIV) and, in particular, the continuous isolation of new Multidrug-resistant strains (MDR), rendering the discovery of novel anti-TB agents a strategic priority. One of the most effective first-line mycobactericidal drugs is Isoniazid (INH). Previously, we reported in vitro anti-mycobacterial activity against sensitive and MDR Mycobacterium tuberculosis strains of a new oxadiazole obtained from the hybridization of INH and palmitic acid. The present study evaluated the therapeutic potential of liposomes including Phosphatidylcholine (PC) and L-α Phosphatidic acid (PA) or PC and Cholesterol (Chol) containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in BALB/c male mice infected by intratracheal (i.t.) route with drug-sensitive or MDR M. tuberculosis. Methods: The lipophilic 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine was obtained to mix INH and palmitoyl chloride. The in vivo anti-TB effect of this oxadiazole derivative contained in two different liposomes was tested in BALB/c mice infected with a sensitive strain of M. tuberculosis, initiating treatment 2 months post-infection, by i.t. route, of 50 μg of oxadiazole derivative for 1 month. In a second stage, mice were infected with an MDR (resistant to first-line drugs) and treated with 150 μg of an oxadiazole derivative carried by PC + Chol liposomes for 2 months. The effect of the oxadiazole derivative in vivo was determined by the quantification of lung bacilli loads and histopathology. Results: In comparison with control animals, drug-sensitive, strain-infected mice treated for 1 month with 50 μg of this oxadiazole derivative contained in the liposomes of PC + Chol showed a significant, 80% decrease of live bacilli in lungs, which correlated with the morphometric observation, and the group of MDR clinical isolate-infected mice treated with 150 μg of the oxadiazole derivative contained in the same type of liposome showed significantly lower lung bacillary loads than control mice, producing 90% of bacilli burden reduction after 2 months of treatment. Conclusion: These results confirm and extend the reported highly efficient anti-mycobacterial activity of this lipophilic oxidazole derivative when it is carried by liposomes in mice suffering from late progressive pulmonary TB induced by drug-sensitive, and most prominently by, MDR strains.

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