The Experts below are selected from a list of 11607 Experts worldwide ranked by ideXlab platform
Gopal K. Khuller - One of the best experts on this subject based on the ideXlab platform.
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inhalable alginate nanoparticles as antitubercular drug carriers against Experimental Tuberculosis
International Journal of Antimicrobial Agents, 2005Co-Authors: A Zahoor, Sadhna Sharma, Gopal K. KhullerAbstract:Pharmacokinetic and chemotherapeutic studies have been carried out with aerosolised alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA). The nanoparticles were prepared by cation-induced gelification of alginate and were 235.5 +/- 0 nm in size, with drug encapsulation efficiencies of 70-90% for INH and PZA and 80-90% for RIF. The majority of particles (80.5%) were in the respirable range, with mass median aerodynamic diameter of 1.1 +/- 0.4 microm and geometric standard deviation of 1.71 +/- 0.1 microm. The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with oral free drugs. All drugs were detected in organs (lungs, liver and spleen) above the minimum inhibitory concentration until 15 days post nebulisation, whilst free drugs stayed up to day 1. The chemotherapeutic efficacy of three doses of drug-loaded alginate nanoparticles nebulised 15 days apart was comparable with 45 daily doses of oral free drugs. Thus, inhalable alginate nanoparticles can serve as an ideal carrier for the controlled release of antitubercular drugs.
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oral solid lipid nanoparticle based antitubercular chemotherapy
Tuberculosis, 2005Co-Authors: Rajesh Pandey, Sadhna Sharma, Gopal K. KhullerAbstract:Summary The present study was planned to evaluate the chemotherapeutic potential of oral solid lipid nanoparticles (SLNs) incorporating rifampicin, isoniazid and pyrazinamide against Experimental Tuberculosis. The SLNs were prepared by the "emulsion solvent diffusion" technique with an encapsulation efficiency of 51±5% for rifampicin, 45±4% for isoniazid and 41±4% for pyrazinamide. Following a single oral administration to mice, therapeutic drug concentrations were maintained in the plasma for 8 days and in the organs (lungs, liver and spleen) for 10 days whereas free drugs were cleared by 1–2 days. In M. tubercuIosis H 37 Rv infected mice, no tubercle bacilli could be detected in the lungs/spleen after 5 oral doses of drug loaded SLNs administered at every 10th day whereas 46 daily doses of oral free drugs were required to obtain an equivalent therapeutic benefit. Thus, SLN based antitubercular drug therapy forms a sound basis for reducing dosing frequency and improving patient compliance for better management of Tuberculosis.
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solid lipid particle based inhalable sustained drug delivery system against Experimental Tuberculosis
Tuberculosis, 2005Co-Authors: Rajesh Pandey, Gopal K. KhullerAbstract:The present study was planned to evaluate the chemotherapeutic potential of nebulized solid lipid particles (SLPs) incorporating rifampicin, isoniazid and pyrazinamide against Experimental Tuberculosis. The SLPs prepared by the "emulsion solvent diffusion" technique possessed a favourable mass median aerodynamic diameter suitable for bronchoalveolar drug delivery. Following a single nebulization to guinea pigs, therapeutic drug concentrations were maintained in the plasma for 5 days and in the organs (lungs, liver and spleen) for 7 days whereas free drugs were cleared by 1-2 days. The mean residence time and drug bioavailability were improved several-fold in the case of drug-loaded SLPs. A similar pharmacokinetic profile was observed in Mycobacterium Tuberculosis-infected guinea pigs. On nebulization of drug-loaded SLPs to infected guinea pigs at every 7th day, no tubercle bacilli could be detected in the lungs/spleen after 7 doses of treatment whereas 46 daily doses of orally administered drugs were required to obtain an equivalent therapeutic benefit. Further, there was no evidence of any biochemical hepatotoxicity. Thus, nebulization of SLP-based antitubercular drugs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary Tuberculosis.
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poly dl lactide co glycolide nanoparticle based inhalable sustained drug delivery system for Experimental Tuberculosis
Journal of Antimicrobial Chemotherapy, 2003Co-Authors: Rajesh Pandey, Sadhna Sharma, Gopal K. Khuller, Abdul Zahoor, Anjali Sharma, B. PrasadAbstract:Objectives: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (DL-lactide-co-glycolide) nanoparticles suit- able for nebulization. Methods: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium Tuberculosis infected guinea pigs. Results: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 ± 0.11 µm, favour- able for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained thera- peutic drug levels in the plasma for 6-8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability (compared to intravenous (iv) administration) was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles contain- ing drugs to M. Tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit.
Rajesh Pandey - One of the best experts on this subject based on the ideXlab platform.
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oral solid lipid nanoparticle based antitubercular chemotherapy
Tuberculosis, 2005Co-Authors: Rajesh Pandey, Sadhna Sharma, Gopal K. KhullerAbstract:Summary The present study was planned to evaluate the chemotherapeutic potential of oral solid lipid nanoparticles (SLNs) incorporating rifampicin, isoniazid and pyrazinamide against Experimental Tuberculosis. The SLNs were prepared by the "emulsion solvent diffusion" technique with an encapsulation efficiency of 51±5% for rifampicin, 45±4% for isoniazid and 41±4% for pyrazinamide. Following a single oral administration to mice, therapeutic drug concentrations were maintained in the plasma for 8 days and in the organs (lungs, liver and spleen) for 10 days whereas free drugs were cleared by 1–2 days. In M. tubercuIosis H 37 Rv infected mice, no tubercle bacilli could be detected in the lungs/spleen after 5 oral doses of drug loaded SLNs administered at every 10th day whereas 46 daily doses of oral free drugs were required to obtain an equivalent therapeutic benefit. Thus, SLN based antitubercular drug therapy forms a sound basis for reducing dosing frequency and improving patient compliance for better management of Tuberculosis.
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solid lipid particle based inhalable sustained drug delivery system against Experimental Tuberculosis
Tuberculosis, 2005Co-Authors: Rajesh Pandey, Gopal K. KhullerAbstract:The present study was planned to evaluate the chemotherapeutic potential of nebulized solid lipid particles (SLPs) incorporating rifampicin, isoniazid and pyrazinamide against Experimental Tuberculosis. The SLPs prepared by the "emulsion solvent diffusion" technique possessed a favourable mass median aerodynamic diameter suitable for bronchoalveolar drug delivery. Following a single nebulization to guinea pigs, therapeutic drug concentrations were maintained in the plasma for 5 days and in the organs (lungs, liver and spleen) for 7 days whereas free drugs were cleared by 1-2 days. The mean residence time and drug bioavailability were improved several-fold in the case of drug-loaded SLPs. A similar pharmacokinetic profile was observed in Mycobacterium Tuberculosis-infected guinea pigs. On nebulization of drug-loaded SLPs to infected guinea pigs at every 7th day, no tubercle bacilli could be detected in the lungs/spleen after 7 doses of treatment whereas 46 daily doses of orally administered drugs were required to obtain an equivalent therapeutic benefit. Further, there was no evidence of any biochemical hepatotoxicity. Thus, nebulization of SLP-based antitubercular drugs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary Tuberculosis.
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poly dl lactide co glycolide nanoparticle based inhalable sustained drug delivery system for Experimental Tuberculosis
Journal of Antimicrobial Chemotherapy, 2003Co-Authors: Rajesh Pandey, Sadhna Sharma, Gopal K. Khuller, Abdul Zahoor, Anjali Sharma, B. PrasadAbstract:Objectives: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (DL-lactide-co-glycolide) nanoparticles suit- able for nebulization. Methods: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium Tuberculosis infected guinea pigs. Results: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 ± 0.11 µm, favour- able for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained thera- peutic drug levels in the plasma for 6-8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability (compared to intravenous (iv) administration) was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles contain- ing drugs to M. Tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit.
Eamonn Gormley - One of the best experts on this subject based on the ideXlab platform.
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Experimental Tuberculosis in the european badger meles meles after endobronchial inoculation with mycobacterium bovis ii progression of infection
Research in Veterinary Science, 2008Co-Authors: L A Corner, Sandrine Lesellier, Eamon Costello, D Omeara, Eamonn GormleyAbstract:Abstract The aim of the study was to describe, over a period of 24 weeks, the pathological and bacteriological changes in badgers Experimentally infected with Mycobacterium bovis. The badgers were infected by endobronchial instillation of 2.5 × 104 colony forming units (cfu) M. bovis. After infection, the badgers were examined at 3 weekly intervals when blood and tracheal aspirates were collected. At 6, 12, 18 and 24 weeks post-infection (pi) three animals were euthanized and a detailed pathological and bacteriological examination was performed to assess the nature of the Experimental disease. During the course of the study only one badger developed clinical signs of disease: a subcutaneous swelling on its head, first observed at 18 weeks pi. At post-mortem examination gross and histological lesions of Tuberculosis were observed and M. bovis was recovered from all, except one badger. In the majority of badgers the endobronchial route of inoculation resulted in the establishment of infection that over 24 weeks was non-progressive with limited dissemination of infection from the thoracic cavity, mainly to the hepatic and mesenteric lymph nodes. However, in one of the badgers examined at 18 weeks pi and one at 24 weeks pi, infection was widely disseminated. The disease induced by the endobronchial inoculation displayed the characteristics of disease observed in naturally infected badgers.
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Experimental Tuberculosis in the european badger meles meles after endobronchial inoculation of mycobacterium bovis i pathology and bacteriology
Research in Veterinary Science, 2007Co-Authors: L A Corner, Sandrine Lesellier, Eamon Costello, D Omeara, D P Sleeman, Eamonn GormleyAbstract:The aim was to develop an endobronchial infection procedure for the study of Mycobacterium bovis infection in badgers. The badgers were anaesthetised and a cannula was passed per os to the tracheal bifurcation. When in place 1 ml of M. bovis suspension was inoculated. Three concentrations of M. bovis suspension were used; <10 colony forming units (cfu), approximately 10(2) cfu and approximately 3 x 10(3) cfu. The badgers were examined at three weekly intervals for clinical signs of disease and a tracheal aspirate was collected at each examination. The badgers were euthanased 17 weeks post infection (pi) and at the post mortem examination a wide range of tissues were examined for gross and histopathological lesions of Tuberculosis and cultured for M. bovis. A sample of bronchial alveolar lavage (BAL) fluid was collected at post mortem for culture. At post mortem examination 17 weeks after infection, gross and histopathological lesions of Tuberculosis were observed in all badgers inoculated with the high and medium dose and 1/3 inoculated with the low dose. M. bovis was recovered from all inoculated badgers. Infection in the high dose group was more widely disseminated than in the other groups. The number of sites with gross and histopathological lesions increased with increasing dose of M. bovis. All tracheal aspirates were negative on culture and only one BAL, collected from a badger of the high dose group, was positive on culture. No clinical signs due to the Experimental infection were observed. The endobronchial route of inoculation is an effective route for establishing Experimental infection, and could be used for studies of Tuberculosis pathogenesis, immunology of M. bovis infection in badgers and for challenging badgers in vaccine protection studies. Badgers appeared to be very susceptible to infection by this procedure even with a dose of < 10 cfu but appear to control and limit the resulting infection.
Sadhna Sharma - One of the best experts on this subject based on the ideXlab platform.
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inhalable alginate nanoparticles as antitubercular drug carriers against Experimental Tuberculosis
International Journal of Antimicrobial Agents, 2005Co-Authors: A Zahoor, Sadhna Sharma, Gopal K. KhullerAbstract:Pharmacokinetic and chemotherapeutic studies have been carried out with aerosolised alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA). The nanoparticles were prepared by cation-induced gelification of alginate and were 235.5 +/- 0 nm in size, with drug encapsulation efficiencies of 70-90% for INH and PZA and 80-90% for RIF. The majority of particles (80.5%) were in the respirable range, with mass median aerodynamic diameter of 1.1 +/- 0.4 microm and geometric standard deviation of 1.71 +/- 0.1 microm. The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with oral free drugs. All drugs were detected in organs (lungs, liver and spleen) above the minimum inhibitory concentration until 15 days post nebulisation, whilst free drugs stayed up to day 1. The chemotherapeutic efficacy of three doses of drug-loaded alginate nanoparticles nebulised 15 days apart was comparable with 45 daily doses of oral free drugs. Thus, inhalable alginate nanoparticles can serve as an ideal carrier for the controlled release of antitubercular drugs.
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oral solid lipid nanoparticle based antitubercular chemotherapy
Tuberculosis, 2005Co-Authors: Rajesh Pandey, Sadhna Sharma, Gopal K. KhullerAbstract:Summary The present study was planned to evaluate the chemotherapeutic potential of oral solid lipid nanoparticles (SLNs) incorporating rifampicin, isoniazid and pyrazinamide against Experimental Tuberculosis. The SLNs were prepared by the "emulsion solvent diffusion" technique with an encapsulation efficiency of 51±5% for rifampicin, 45±4% for isoniazid and 41±4% for pyrazinamide. Following a single oral administration to mice, therapeutic drug concentrations were maintained in the plasma for 8 days and in the organs (lungs, liver and spleen) for 10 days whereas free drugs were cleared by 1–2 days. In M. tubercuIosis H 37 Rv infected mice, no tubercle bacilli could be detected in the lungs/spleen after 5 oral doses of drug loaded SLNs administered at every 10th day whereas 46 daily doses of oral free drugs were required to obtain an equivalent therapeutic benefit. Thus, SLN based antitubercular drug therapy forms a sound basis for reducing dosing frequency and improving patient compliance for better management of Tuberculosis.
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poly dl lactide co glycolide nanoparticle based inhalable sustained drug delivery system for Experimental Tuberculosis
Journal of Antimicrobial Chemotherapy, 2003Co-Authors: Rajesh Pandey, Sadhna Sharma, Gopal K. Khuller, Abdul Zahoor, Anjali Sharma, B. PrasadAbstract:Objectives: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (DL-lactide-co-glycolide) nanoparticles suit- able for nebulization. Methods: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium Tuberculosis infected guinea pigs. Results: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 ± 0.11 µm, favour- able for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained thera- peutic drug levels in the plasma for 6-8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability (compared to intravenous (iv) administration) was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles contain- ing drugs to M. Tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit.
L A Corner - One of the best experts on this subject based on the ideXlab platform.
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Experimental Tuberculosis in the european badger meles meles after endobronchial inoculation with mycobacterium bovis ii progression of infection
Research in Veterinary Science, 2008Co-Authors: L A Corner, Sandrine Lesellier, Eamon Costello, D Omeara, Eamonn GormleyAbstract:Abstract The aim of the study was to describe, over a period of 24 weeks, the pathological and bacteriological changes in badgers Experimentally infected with Mycobacterium bovis. The badgers were infected by endobronchial instillation of 2.5 × 104 colony forming units (cfu) M. bovis. After infection, the badgers were examined at 3 weekly intervals when blood and tracheal aspirates were collected. At 6, 12, 18 and 24 weeks post-infection (pi) three animals were euthanized and a detailed pathological and bacteriological examination was performed to assess the nature of the Experimental disease. During the course of the study only one badger developed clinical signs of disease: a subcutaneous swelling on its head, first observed at 18 weeks pi. At post-mortem examination gross and histological lesions of Tuberculosis were observed and M. bovis was recovered from all, except one badger. In the majority of badgers the endobronchial route of inoculation resulted in the establishment of infection that over 24 weeks was non-progressive with limited dissemination of infection from the thoracic cavity, mainly to the hepatic and mesenteric lymph nodes. However, in one of the badgers examined at 18 weeks pi and one at 24 weeks pi, infection was widely disseminated. The disease induced by the endobronchial inoculation displayed the characteristics of disease observed in naturally infected badgers.
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Experimental Tuberculosis in the european badger meles meles after endobronchial inoculation of mycobacterium bovis i pathology and bacteriology
Research in Veterinary Science, 2007Co-Authors: L A Corner, Sandrine Lesellier, Eamon Costello, D Omeara, D P Sleeman, Eamonn GormleyAbstract:The aim was to develop an endobronchial infection procedure for the study of Mycobacterium bovis infection in badgers. The badgers were anaesthetised and a cannula was passed per os to the tracheal bifurcation. When in place 1 ml of M. bovis suspension was inoculated. Three concentrations of M. bovis suspension were used; <10 colony forming units (cfu), approximately 10(2) cfu and approximately 3 x 10(3) cfu. The badgers were examined at three weekly intervals for clinical signs of disease and a tracheal aspirate was collected at each examination. The badgers were euthanased 17 weeks post infection (pi) and at the post mortem examination a wide range of tissues were examined for gross and histopathological lesions of Tuberculosis and cultured for M. bovis. A sample of bronchial alveolar lavage (BAL) fluid was collected at post mortem for culture. At post mortem examination 17 weeks after infection, gross and histopathological lesions of Tuberculosis were observed in all badgers inoculated with the high and medium dose and 1/3 inoculated with the low dose. M. bovis was recovered from all inoculated badgers. Infection in the high dose group was more widely disseminated than in the other groups. The number of sites with gross and histopathological lesions increased with increasing dose of M. bovis. All tracheal aspirates were negative on culture and only one BAL, collected from a badger of the high dose group, was positive on culture. No clinical signs due to the Experimental infection were observed. The endobronchial route of inoculation is an effective route for establishing Experimental infection, and could be used for studies of Tuberculosis pathogenesis, immunology of M. bovis infection in badgers and for challenging badgers in vaccine protection studies. Badgers appeared to be very susceptible to infection by this procedure even with a dose of < 10 cfu but appear to control and limit the resulting infection.
