The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform
Carola Aguzzi - One of the best experts on this subject based on the ideXlab platform.
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Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment.
Journal of biomedical materials research. Part A, 2019Co-Authors: E. Carazo, Giuseppina Sandri, Pilar Cerezo, Cristina Lanni, Franca Ferrari, Cristina Bonferoni, César Viseras, Carola AguzziAbstract:Halloysite nanotubes (HLNTs) were used as nanocarriers of the Tuberculostatic Agent isoniazid (INH), a BCS (Biopharmaceutics Classification System) class III drug. Self-assembling nanohybrids (INH-loaded HLNTs) with an average outer diameter of 90 nm and polydispersity index of 0.7 approximately, were obtained by spontaneous adsorption of INH molecules to HLNTs powder in aqueous medium. The nanohybrids were aimed to improve oral drug bioavailability and reduce physicochemical incompatibility of INH with other concomitantly administered Tuberculostatic Agents. In vitro drug release from INH-loaded HLNTs was successfully fitted to a diffusive kinetic law founded on the adsorption-desorption equilibrium between drug molecules in solution and solid inorganic excipients. INH-loaded HLNTs showed good in vitro biocompatibility toward Caco-2 cells at the concentrations studied (up to 1233 μg/mL), with improved cell proliferation. Permeability tests showed that INH transport across Caco-2 cellular membranes was greatly enhanced and fluorescent microscopy confirmed that the drug encapsulated into nanohybrid was effectively internalized by the cells. INH-loaded HLNTs enhanced stability of the drug in presence of other Tuberculostatic Agents, both in binary and quaternary combinations. It has been demonstrated that simple interaction between INH with HLNTs leads to drug permeability and stability improvements that could greatly facilitate the design of multiple drug dosage forms, an actual challenge in oral treatment of tuberculosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
Thadeu Estevam Moreira Maramaldo Costa - One of the best experts on this subject based on the ideXlab platform.
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mefloquine oxazolidine derivatives derived from mefloquine and arenecarbaldehydes in vitro activity including against the multidrug resistant tuberculosis strain t113
Bioorganic & Medicinal Chemistry, 2012Co-Authors: Raoni S B Goncalves, Carlos R Kaiser, Maria C S Lourenco, Flavio A F M Bezerra, Marcus V N De Souza, James L Wardell, Solange M S V Wardell, Maria Das Gracas M O Henriques, Thadeu Estevam Moreira Maramaldo CostaAbstract:Ten new mefloquine-oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl=substituted phenyl) and 4-[(1S,8aR)-3-(heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline [2: heteroaryl=5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl=3-ethoxyphenyl), 1g (Ar=3,4,5-(MeO)(3)-C(6)H(2)) and 2c were slightly more active than mefloquine (MIC=33μM) with MICs=24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl=3,4-(MeO)(2)-C(6)H(3)) and 2a (MICs=11.9 and 12.1μM, respectively) were ca. 2.7 times more active than mefloquine, with a better Tuberculostatic activity than the first line Tuberculostatic Agent ethambutol (MIC=15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values.
Marcus V N De Souza - One of the best experts on this subject based on the ideXlab platform.
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mefloquine oxazolidine derivatives derived from mefloquine and arenecarbaldehydes in vitro activity including against the multidrug resistant tuberculosis strain t113
Bioorganic & Medicinal Chemistry, 2012Co-Authors: Raoni S B Goncalves, Carlos R Kaiser, Maria C S Lourenco, Flavio A F M Bezerra, Marcus V N De Souza, James L Wardell, Solange M S V Wardell, Maria Das Gracas M O Henriques, Thadeu Estevam Moreira Maramaldo CostaAbstract:Ten new mefloquine-oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl=substituted phenyl) and 4-[(1S,8aR)-3-(heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline [2: heteroaryl=5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl=3-ethoxyphenyl), 1g (Ar=3,4,5-(MeO)(3)-C(6)H(2)) and 2c were slightly more active than mefloquine (MIC=33μM) with MICs=24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl=3,4-(MeO)(2)-C(6)H(3)) and 2a (MICs=11.9 and 12.1μM, respectively) were ca. 2.7 times more active than mefloquine, with a better Tuberculostatic activity than the first line Tuberculostatic Agent ethambutol (MIC=15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values.
C A Peloquin - One of the best experts on this subject based on the ideXlab platform.
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direct lung delivery of para aminosalicylic acid by aerosol particles
Tuberculosis, 2003Co-Authors: Nicolas Tsapis, D Bennett, K Odriscoll, K Shea, M M Lipp, R W Clarke, D Deaver, Daniel Yamins, James C Wright, C A PeloquinAbstract:Para-aminosalicylic acid (PAS), a Tuberculostatic Agent, was formulated into large porous particles for direct delivery into the lungs via inhalation. These particles possess optimized physical properties for deposition throughout the respiratory tract, a drug loading of 95% by weight and physical stability over 4 weeks at elevated temperatures. Upon insufflation in rats, PAS concentrations were measured in plasma, lung lining fluid and homogenized whole lung tissue. Systemic drug concentrations peaked at 15 min, with a maximum plasma concentration of 11+/-1 microg/ml. The concentration in the lung lining fluid was 148+/-62 microg/ml at 15 min. Tissue concentrations were 65+/-20 microg/ml at 15 min and 3.2+/-0.2 microg/ml at 3h. PAS was cleared within 3 h from the lung lining fluid and plasma but was still present at therapeutic concentrations in the lung tissue. These results suggest that inhalation delivery of PAS can potentially allow for a reduction in total dose delivered while providing for higher local and similar peak systemic drug concentrations as compared to those obtained upon oral PAS dosing. Similar particles could potentially be used for the delivery of additional anti-tuberculosis Agents such as rifampicin, aminoglucosides or fluoroquinolones.
E. Carazo - One of the best experts on this subject based on the ideXlab platform.
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Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment.
Journal of biomedical materials research. Part A, 2019Co-Authors: E. Carazo, Giuseppina Sandri, Pilar Cerezo, Cristina Lanni, Franca Ferrari, Cristina Bonferoni, César Viseras, Carola AguzziAbstract:Halloysite nanotubes (HLNTs) were used as nanocarriers of the Tuberculostatic Agent isoniazid (INH), a BCS (Biopharmaceutics Classification System) class III drug. Self-assembling nanohybrids (INH-loaded HLNTs) with an average outer diameter of 90 nm and polydispersity index of 0.7 approximately, were obtained by spontaneous adsorption of INH molecules to HLNTs powder in aqueous medium. The nanohybrids were aimed to improve oral drug bioavailability and reduce physicochemical incompatibility of INH with other concomitantly administered Tuberculostatic Agents. In vitro drug release from INH-loaded HLNTs was successfully fitted to a diffusive kinetic law founded on the adsorption-desorption equilibrium between drug molecules in solution and solid inorganic excipients. INH-loaded HLNTs showed good in vitro biocompatibility toward Caco-2 cells at the concentrations studied (up to 1233 μg/mL), with improved cell proliferation. Permeability tests showed that INH transport across Caco-2 cellular membranes was greatly enhanced and fluorescent microscopy confirmed that the drug encapsulated into nanohybrid was effectively internalized by the cells. INH-loaded HLNTs enhanced stability of the drug in presence of other Tuberculostatic Agents, both in binary and quaternary combinations. It has been demonstrated that simple interaction between INH with HLNTs leads to drug permeability and stability improvements that could greatly facilitate the design of multiple drug dosage forms, an actual challenge in oral treatment of tuberculosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
