The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Jeanchristophe Olivier - One of the best experts on this subject based on the ideXlab platform.
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formulation of Rifampicin cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Jeanchristophe Olivier, Julien Brillault, William CouetAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
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Formulation of Rifampicin–cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Julien Brillault, William Couet, Jeanchristophe OlivierAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
William Couet - One of the best experts on this subject based on the ideXlab platform.
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formulation of Rifampicin cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Jeanchristophe Olivier, Julien Brillault, William CouetAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
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Formulation of Rifampicin–cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Julien Brillault, William Couet, Jeanchristophe OlivierAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
Julien Brillault - One of the best experts on this subject based on the ideXlab platform.
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formulation of Rifampicin cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Jeanchristophe Olivier, Julien Brillault, William CouetAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
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Formulation of Rifampicin–cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Julien Brillault, William Couet, Jeanchristophe OlivierAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
Frederic Tewes - One of the best experts on this subject based on the ideXlab platform.
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formulation of Rifampicin cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Jeanchristophe Olivier, Julien Brillault, William CouetAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
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Formulation of Rifampicin–cyclodextrin complexes for lung nebulization
Journal of Controlled Release, 2008Co-Authors: Frederic Tewes, Julien Brillault, William Couet, Jeanchristophe OlivierAbstract:Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like Rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated Rifampicin–CD complexes in terms of Rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between Rifampicin and methylated β-cyclodextrin (RAMEB) or hydroxypropyl-β-cyclodextrin (HPβCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an AL-type curve for RAMEB and a BS-type for HPβCD. Stability constants calculated for a 1:1 molar ratio of CD/Rifampicin were 73.4 ± 8.2 M− 1 for RAMEB and 68.5 ± 5.2 M− 1 for HPβCD. Complexes with RAMEB or HPβCD increased 22 times and 7.6 times respectively the apparent solubility of Rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPβCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPβCD complexes measured by the total Rifampicin MIC against A. baumannii was similar or lower to free Rifampicin MIC respectively. Complexation did not alter the Rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for Rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active Rifampicin and optimize its lung pharmacokinetic profile.
Emma Claire Louise Marrs - One of the best experts on this subject based on the ideXlab platform.
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mode of action of kanglemycin a an ansamycin natural product that is active against Rifampicin resistant mycobacterium tuberculosis
Molecular Cell, 2018Co-Authors: Hamed Mosaei, Vadim Molodtsov, Bernhard Kepplinger, John Harbottle, Christopher William Moon, Lucia Ceccaroni, Yeonoh Shin, Stephanie Mortonlaing, Rose E. Jeeves, Emma Claire Louise MarrsAbstract:Antibiotic-resistant bacterial pathogens pose an urgent healthcare threat, prompting a demand for new medicines. We report the mode of action of the natural ansamycin antibiotic kanglemycin A (KglA). KglA binds bacterial RNA polymerase at the Rifampicin-binding pocket but maintains potency against RNA polymerases containing Rifampicin-resistant mutations. KglA has antibiotic activity against Rifampicin-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis (MDR-M. tuberculosis). The X-ray crystal structures of KglA with the Escherichia coli RNA polymerase holoenzyme and Thermus thermophilus RNA polymerase-promoter complex reveal an altered—compared with Rifampicin—conformation of KglA within the Rifampicin-binding pocket. Unique deoxysugar and succinate ansa bridge substituents make additional contacts with a separate, hydrophobic pocket of RNA polymerase and preclude the formation of initial dinucleotides, respectively. Previous ansa-chain modifications in the rifamycin series have proven unsuccessful. Thus, KglA represents a key starting point for the development of a new class of ansa-chain derivatized ansamycins to tackle Rifampicin resistance.
