A high throughput ultra pressure liquid chromatography-mass spectrometry (UPLC-MS/MS) method with good sensitivity and selectivity has been developed and validated for simultaneous quantification of esomeprazole, ra...A high throughput ultra pressure liquid chromatography-mass spectrometry (UPLC-MS/MS) method with good sensitivity and selectivity has been developed and validated for simultaneous quantification of esomeprazole, rabeprazole and levosulpiride in human plasma using lansoprazole as internal standard (IS). The extraction method based on liquid-liquid extraction technique was used to extract the analytes and IS from of 50 μL of human plasma using methyl tert-butyl ether:ethyl acetate (80:20, v/v), which offers a high recovery. Chromatographic separation of analytes and IS was achieved on a Hypersil gold C18 column using gradient mobile phase consisting of 2 mM ammonium formate/acetonitrile. The flow rate was set at 0.5 mL/min to elute all the analytes and IS within 1.00 min runtime. Detection of target compounds was performed on a triple quadruple mass spectrometer by multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). Method validation results demonstrated that the developed method has good precision and accuracy over the concentration ranges of 0.1-2000 ng/mL for each analyte. Stability of compounds was established in a battery of stability studies, i.e., bench top, autosampler, dry extract and long-term storage stability as well as freeze-thaw cycles. The validated method has been successfully applied to analyze human plasma samples for application in pharmaco- kinetic studies.展开更多
In the primitive era, humans benefited partially from plants and metals to treat microbial infections. Later these infections were cured with antibiotics but further suffered from resistance issues. In searching of an...In the primitive era, humans benefited partially from plants and metals to treat microbial infections. Later these infections were cured with antibiotics but further suffered from resistance issues. In searching of an alternative, researchers developed an adjuvant therapy but were hampered by spreading resistance. Subsequently, nanoparticles(NPs) were proposed to cease the multi-drug resistant bacteria but were hindered due to toxicity issues. Recently, a novel adjuvant therapy employed metals and botanicals into innovative nanotechnology as nano-antibiotics. The combination of green synthesized metallic NPs with antibiotics seems to be a viable platform to combat against MDR bacteria by alleviating resistance and toxicity. This review focuses on the primitive to present era dealings with bacterial resistance mechanisms, newer innovations of nanotechnology and their multiple mechanisms to combat resistance. In addition, special focus is paid on greener NPs as antibiotic carriers, and their future prospects of controlled release and toxicity study.展开更多
Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GE...Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GES-1),and to explore the mechanism of EtAc-LME induced apoptosis.Methods:The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases,PARP cleavage,expression of cytochrome-c (Cyt-c) was determined by western blotting,mRNA expression of Bcl-2,Bax by RT-PCR,loss of mitochondrial potential using DiOC6 dye,annexin binding assay and its influence on cell cycle arrest by flow cytometry.Results:The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells(NUCC and MKN-74) compared to normal gastric cells(GES-1),suggesting more specific cytotoxicity to the malignant cells.Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.Conclusions:The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.展开更多
The purpose of this research was to apply statistical design for the preparation of a gastric floating tablet(GFT)of propranolol HCl and to investigate the effect of formulation variables on drug release and the buoya...The purpose of this research was to apply statistical design for the preparation of a gastric floating tablet(GFT)of propranolol HCl and to investigate the effect of formulation variables on drug release and the buoyancy properties of the delivery system.The contents of polyethylene oxide(PEO)WSR coagulant and sodium bicarbonate were used as independent variables in central composite design of the best formulation.Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical model approach showing that both independent variables have significant effects on floating lag time,%drug release at 1 h(D_(1h))and time required to release 90%of the drug(t_(90)).The desired function was used to optimize the response variables,each with a different target,and the observed responses were in good agreement with the experimental values.FTIR and DSC studies of the statistically optimized formulation revealed there was no chemical interaction between drug and polymer.The statistically optimized formulation released drug according to first order kinetics with a non-Fickian diffusion mechanism.Evaluation of the optimized formulation in vivo in human volunteers showed that the GFT was buoyant in gastric fluid and that its gastric residence time was enhanced in the fed but not the fasted state.展开更多
Paracetamol(PCM) hepatotoxicity is related to reactive oxygen species(ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the h...Paracetamol(PCM) hepatotoxicity is related to reactive oxygen species(ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the hepatoprotective activity of an alcoholic extract of Boswellia ovalifoliolata(BO) bark against PCM-induced hepatotoxicity. BO extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2, 2-diphenyl-1-picrylhydrazyl. Administration of PCM caused a significant increase in the release of transaminases, alkaline phosphatase, and lactate dehydrogenase in serum. Significant enhancement in hepatic lipid peroxidation and marked depletion in reduced glutathione were observed after parac intoxication with severe alterations in liver histology. BO treatment was able to mitigate hepatic damage induced by acute intoxication of PCM and showed a pronounced protective effect against lipid peroxidation, deviated serum enzymatic variables, and maintained glutathione status toward control. The results clearly demonstrate the hepatoprotective effect of BO against the toxicity induced by PCM.展开更多
文摘A high throughput ultra pressure liquid chromatography-mass spectrometry (UPLC-MS/MS) method with good sensitivity and selectivity has been developed and validated for simultaneous quantification of esomeprazole, rabeprazole and levosulpiride in human plasma using lansoprazole as internal standard (IS). The extraction method based on liquid-liquid extraction technique was used to extract the analytes and IS from of 50 μL of human plasma using methyl tert-butyl ether:ethyl acetate (80:20, v/v), which offers a high recovery. Chromatographic separation of analytes and IS was achieved on a Hypersil gold C18 column using gradient mobile phase consisting of 2 mM ammonium formate/acetonitrile. The flow rate was set at 0.5 mL/min to elute all the analytes and IS within 1.00 min runtime. Detection of target compounds was performed on a triple quadruple mass spectrometer by multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). Method validation results demonstrated that the developed method has good precision and accuracy over the concentration ranges of 0.1-2000 ng/mL for each analyte. Stability of compounds was established in a battery of stability studies, i.e., bench top, autosampler, dry extract and long-term storage stability as well as freeze-thaw cycles. The validated method has been successfully applied to analyze human plasma samples for application in pharmaco- kinetic studies.
文摘In the primitive era, humans benefited partially from plants and metals to treat microbial infections. Later these infections were cured with antibiotics but further suffered from resistance issues. In searching of an alternative, researchers developed an adjuvant therapy but were hampered by spreading resistance. Subsequently, nanoparticles(NPs) were proposed to cease the multi-drug resistant bacteria but were hindered due to toxicity issues. Recently, a novel adjuvant therapy employed metals and botanicals into innovative nanotechnology as nano-antibiotics. The combination of green synthesized metallic NPs with antibiotics seems to be a viable platform to combat against MDR bacteria by alleviating resistance and toxicity. This review focuses on the primitive to present era dealings with bacterial resistance mechanisms, newer innovations of nanotechnology and their multiple mechanisms to combat resistance. In addition, special focus is paid on greener NPs as antibiotic carriers, and their future prospects of controlled release and toxicity study.
基金The authors are grateful to the Principal,A.U.College of Pharmaceutical Sciences,Andhra University,Visakhapatnam,India for providing necessary facilities to carry out the work.
文摘Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GES-1),and to explore the mechanism of EtAc-LME induced apoptosis.Methods:The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases,PARP cleavage,expression of cytochrome-c (Cyt-c) was determined by western blotting,mRNA expression of Bcl-2,Bax by RT-PCR,loss of mitochondrial potential using DiOC6 dye,annexin binding assay and its influence on cell cycle arrest by flow cytometry.Results:The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells(NUCC and MKN-74) compared to normal gastric cells(GES-1),suggesting more specific cytotoxicity to the malignant cells.Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.Conclusions:The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.
基金The author M.V.Srikanth is thankful to the University Grants Commission,India for awarding a Senior Research Fellowship to carry out this project.
文摘The purpose of this research was to apply statistical design for the preparation of a gastric floating tablet(GFT)of propranolol HCl and to investigate the effect of formulation variables on drug release and the buoyancy properties of the delivery system.The contents of polyethylene oxide(PEO)WSR coagulant and sodium bicarbonate were used as independent variables in central composite design of the best formulation.Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical model approach showing that both independent variables have significant effects on floating lag time,%drug release at 1 h(D_(1h))and time required to release 90%of the drug(t_(90)).The desired function was used to optimize the response variables,each with a different target,and the observed responses were in good agreement with the experimental values.FTIR and DSC studies of the statistically optimized formulation revealed there was no chemical interaction between drug and polymer.The statistically optimized formulation released drug according to first order kinetics with a non-Fickian diffusion mechanism.Evaluation of the optimized formulation in vivo in human volunteers showed that the GFT was buoyant in gastric fluid and that its gastric residence time was enhanced in the fed but not the fasted state.
文摘Paracetamol(PCM) hepatotoxicity is related to reactive oxygen species(ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the hepatoprotective activity of an alcoholic extract of Boswellia ovalifoliolata(BO) bark against PCM-induced hepatotoxicity. BO extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2, 2-diphenyl-1-picrylhydrazyl. Administration of PCM caused a significant increase in the release of transaminases, alkaline phosphatase, and lactate dehydrogenase in serum. Significant enhancement in hepatic lipid peroxidation and marked depletion in reduced glutathione were observed after parac intoxication with severe alterations in liver histology. BO treatment was able to mitigate hepatic damage induced by acute intoxication of PCM and showed a pronounced protective effect against lipid peroxidation, deviated serum enzymatic variables, and maintained glutathione status toward control. The results clearly demonstrate the hepatoprotective effect of BO against the toxicity induced by PCM.