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Détails du magazine
Format
Magazine
eISSN
1846-9558
Première publication
28 Feb 2007
Période de publication
4 fois par an
Langues
Anglais

Chercher

Volume 70 (2020): Edition 3 (September 2020)

Détails du magazine
Format
Magazine
eISSN
1846-9558
Première publication
28 Feb 2007
Période de publication
4 fois par an
Langues
Anglais

Chercher

10 Articles
Accès libre

2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses

Publié en ligne: 17 Feb 2020
Pages: 259 - 290

Résumé

Abstract

Parasitic diseases are a serious public health problem affecting hundreds of millions of people worldwide. African trypanosomiasis, American trypanosomiasis, leishmaniasis, malaria and toxoplasmosis are the main parasitic infections caused by protozoan parasites with over one million deaths each year. Due to old medications and drug resistance worldwide, there is an urgent need for new antiparasitic drugs. 1,3,4-Thiadiazoles have been widely studied for medical applications. The chemical, physical and pharmacokinetic properties recommend 1,3,4-thiadiazole ring as a target in drug development. Many scientific papers report the antiparasitic potential of 2-amino-1,3,4-thiadiazoles. This review presents synthetic 2-amino-1,3,4-thiadiazoles exhibiting antitrypanosomal, antimalarial and antitoxoplasmal activities. Although there are insufficient results to state the quality of 2-amino-1,3,4-thiadiazoles as a new class of antiparasitic agents, many reported derivatives can be considered as lead compounds for drug synthesis and a promise for the future treatment of parasitosis and provide a valid strategy for the development of potent antiparasitic drugs.

Mots clés

  • 2-amino-1
  • 3
  • 4-thiadiazoles
  • antiparasitic activity
  • anti-trypanosomal activity
  • antimalarial activity
  • antitoxoplasmal activity
  • inhibitory concentration
Accès libre

Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

Publié en ligne: 17 Feb 2020
Pages: 291 - 301

Résumé

Abstract

Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy.

Mots clés

  • valproic acid
  • short-chain fatty acids
  • anticancer activities
  • histone deacetylase inhibitors
  • pre-clinical and clinical studies
Accès libre

Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones

Publié en ligne: 17 Feb 2020
Pages: 303 - 324

Résumé

Abstract

Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assuring about 59–93 % yield, low harmful emissions and reagent economy. The structures of the new compounds were elucidated by melting points, TLC characteristics, IR, 1H and 13C NMR spectral data followed by MS data. The purity of the obtained compounds was proven by the corresponding elemental analyses. “Lipinski’s rule of five” parameters were applied for preliminary evaluation of the pharmacokinetic properties of the target molecules. The initial in vitro safety screening for cytotoxicity (on HepG2 cells) and hemocompatibility (hemolysis assay) showed good safety of the new compounds, where ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene)-hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyr-role-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2-hydroxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan--2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4a) were the least toxic. The antioxidant activity in terms of radical scavenging activity (DPPH test) and reducing ability (ABTS) was also evaluated. The antioxidant protective potential of the compounds was next determined in different in vitro cellular-based models, revealing compounds 4d and 3 [ethyl 5-(4-bromophenyl)-1-(1-hydrazineyl-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate] as the most promising compounds, with 4d having better safety profile.

Mots clés

  • pyrrole hydrazones
  • DPPH
  • ABTS
  • cytotoxicity
  • micro-somes
  • oxidative stress
Accès libre

Stability study of thymoquinone, carvacrol and thymol using HPLC-UV and LC-ESI-MS

Publié en ligne: 17 Feb 2020
Pages: 325 - 342

Résumé

Abstract

The aim of this study was to investigate the stability of three major antioxidants of Nigella sativa: thymoquinone (TQ), carvacrol (CR) and thymol (THY), under different stress conditions using HPLC and LC-MS/MS. Forced degradation for each compound was performed under different conditions, including oxidation, hydrolysis, photolysis and thermal decomposition. The results showed that both CR and THY were stable under the studied conditions, whereas TQ was not affected by acidic, basic and oxidative forced conditions but the effect of light and heat was significant. The degradation products of TQ were further investigated and characterized by LC-MS/MS. HPLC-UV method has been fully validated in terms of linearity and range, the limit of detection and quantitation, precision, selectivity, accuracy and robustness. The method was successfully applied to quantitative analysis of the principal antioxidants of Nigella sativa TQ, CR and THY in different phytopharmaceuticals.

Mots clés

  • thymoquinone
  • carvacrol
  • thymol
  • HPLC-UV
  • LC-MS/MS
  • stability
Accès libre

Simultaneous determination of warfarin and 7-hydroxywarfarin in rat plasma by HPLC-FLD

Publié en ligne: 17 Feb 2020
Pages: 343 - 357

Résumé

Abstract

In this study, high-performance liquid chromatography with fluorescence detection (HPLC-FLD) has been used for the first time, for direct determination of warfarin and its major metabolite, 7-hydroxywarfarin, in rat plasma. The simple and sensitive method was developed using Fortis® reversed-phase diphenyl column (150 × 4.6 mm, 3 μm) and a mobile phase composed of phosphate buffer (25 mmol L−1)/methanol/acetonitrile (70:20:10, V/V/V), adjusted to pH 7.4, at a flow rate of 0.8 mL min−1. The diphenyl chemistry of the stationary phase provided a unique selectivity for separating the structurally related aromatic analytes, warfarin and 7-hydroxywarfarin, allowing their successful quantification in the complex plasma matrix. The method was linear over the range 0.01–25 μg mL−1, for warfarin and 7-hydroxywarfarin, and was found to be accurate, precise and selective in accordance with US FDA guidance for bioanalytical method validation. The method was sensitive enough to quantify 0.01 μg mL−1 of warfarin and 7-hydroxywarfarin (LLOQ) using only 100 μL of plasma. The applicability of this method was demonstrated by analyzing samples obtained from rats after oral administration of a single warfarin dose, and studying warfarin and 7-hydroxywarfarin pharmacokinetics.

Mots clés

  • warfarin
  • 7-hydroxywarfarin
  • high-performance liquid chromatography-fluorescence detection
  • rat plasma
  • pharmacokinetics
Accès libre

Advanced flow cell design for in vitro release testing of mucoadhesive buccal films

Publié en ligne: 17 Feb 2020
Pages: 359 - 371

Résumé

Abstract

Films for buccal application are a slowly emerging new platform for drug delivery. There remains a lack of analytical techniques for the determination of in vitro active pharmaceutical ingredient release. The aim here was to develop an alternative method to the commonly used United States Pharmacopoeia (USP) 2 method, based on the flow-through cell. This system extends the release time and enables more detailed sample discrimination according to formulation. It could be used as a tool for in vivo prediction of drug release rates from buccal film formulations. The flow cell contains two chambers separated by a membrane through which the released active pharmaceutical ingredient is measured. Vital system variables and their effects on the release rate of the model active pharmaceutical ingredient are presented for formulations based on sodium alginate polymer. The method reflects the differences between films and is shown to be discriminatory for evaluation of buccal formulations.

Mots clés

  • release rate
  • buccal films
  • hydrostatic pressure
  • flow cell
Accès libre

Simultaneous spectrofluorometric analysis of tablets containing hydrochlorothiazide combined with timolol maleate or amiloride hydrochloride

Publié en ligne: 17 Feb 2020
Pages: 373 - 385

Résumé

Abstract

Green and sensitive spectrofluorometric methods have been developed and validated for the determination of timolol maleate (TML)/hydrochlorothiazide (HCT) and amiloride hydrochloride (AMH)/hydrochlorothiazide in tablets. The proposed spectrofluorometric procedures were found to be linear in the range of 4–12, 5–35 and 0.025–0.2 mg L−1 for HCT, TML and AMH, resp. The excitation and emission wavelengths for HCT, TML and AMH at room temperature were 270 and 375, 295 and 435, 330 and 415 nm, resp. The methods were validated with respect to ICH guidelines. The AMH showed higher sensitivity with lower values of LOD and LOQ values compared to HCT and TML. The proposed methods were applied to two pharmaceutical formulations; the method for HCT and AMH has proven as reliable assaying method, whereas the method for TML, when combined with HCT, is applicable to screening semi-quantitative analyses.

Mots clés

  • hydrochlorothiazide
  • amiloride hydrochloride
  • timolol maleate
  • fixed-dose combinations
  • spectrofluorometry
  • assaying
  • screening
Accès libre

Differential effects of acute and chronic treatment with the flavonoid chrysin on anxiety-like behavior and Fos immunoreactivity in the lateral septal nucleus in rats

Publié en ligne: 17 Feb 2020
Pages: 387 - 397

Résumé

Abstract

The aim of this study was to compare the effects of acute (a single injection) and chronic (21 consecutive days) treatments with chrysin 2, 4, and 8 μmol kg−1 on anxiety-like behavior and Fos immunoreactivity in the lateral septum nucleus (LSN), a structure that is involved in the regulation of anxiety, in male Wistar rats. These effects were compared with the clinically effective anxiolytic diazepam 7 μmol kg−1. The results showed that acute, but not chronic treatment, with 4 μmol kg−1 chrysin exerted anxiolytic- and anti- depressant-like effects with these effects being similar to that of diazepam. Also, none of the above-mentioned treatments did alter Fos immunoreactivity in the LSN, but a tendency towards the reduction of this variable was detected with chrysin 4 μmol kg−1 and diazepam 7 μmol kg−1. Altogether, results suggest that chrysin exerts anxiolytic-like effects, however, it can produce pharmacological tolerance after repeated use, similar to benzodiazepines.

Mots clés

  • chrysin
  • anxiolytic
  • elevated plus maze
  • Fos protein
  • lateral septal nucleus
Accès libre

Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway

Publié en ligne: 17 Feb 2020
Pages: 399 - 409

Résumé

Abstract

Curcumin has been proved to inhibit cell proliferation and induce cell apoptosis in non-small cell lung cancer (NSCLC). However, little is known about antimetastatic effects and molecular mechanisms of curcumin in NSCLC. In this study, we investigated the involvement of miR-206 in curcumin’s anti-invasion and anti-migration in NSCLC. Cell proliferation was determined by MTT assay. Cell migration and invasion were analyzed by wound healing assay and transwell assay. MiRNA-206 expression was detected by real-time PCR. Western blot was used to detect the protein expression of PI3K/AKT/mTOR signaling pathway. Curcumin significantly inhibited migration and invasion in A549 cells, accompanied by significantly elevated miR-206 expression. Overexpression of miR-206 could inhibit migration and invasion of A549 cells, but it could also significantly decrease the phosphorylation levels of mTOR and AKT. The inhibition of miR-206 promoted cell migration, invasion and increased the phosphorylation level of mTOR and AKT. Furthermore, miR-206 mimics improved the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT in A549 cells. On the contrary, MiR-206 inhibitors reversed the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT. In conclusion, curcumin inhibited cell invasion and migration in NSCLC by elevating the expression of miR-206 which further suppressed the activation of the PI3K/AKT/mTOR pathway.

Mots clés

  • curcumin
  • NSCLC
  • microRNAs
  • migration and invasion
Accès libre

Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride

Publié en ligne: 17 Feb 2020
Pages: 411 - 422

Résumé

Abstract

Donepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-β-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer’s disease due to its higher bioavailability and better distribution to brain when compared to oral route.

Mots clés

  • donepezil hydrochloride
  • thermosensitive gel
  • nasal delivery
  • bioavailability
  • brain targeting
10 Articles
Accès libre

2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses

Publié en ligne: 17 Feb 2020
Pages: 259 - 290

Résumé

Abstract

Parasitic diseases are a serious public health problem affecting hundreds of millions of people worldwide. African trypanosomiasis, American trypanosomiasis, leishmaniasis, malaria and toxoplasmosis are the main parasitic infections caused by protozoan parasites with over one million deaths each year. Due to old medications and drug resistance worldwide, there is an urgent need for new antiparasitic drugs. 1,3,4-Thiadiazoles have been widely studied for medical applications. The chemical, physical and pharmacokinetic properties recommend 1,3,4-thiadiazole ring as a target in drug development. Many scientific papers report the antiparasitic potential of 2-amino-1,3,4-thiadiazoles. This review presents synthetic 2-amino-1,3,4-thiadiazoles exhibiting antitrypanosomal, antimalarial and antitoxoplasmal activities. Although there are insufficient results to state the quality of 2-amino-1,3,4-thiadiazoles as a new class of antiparasitic agents, many reported derivatives can be considered as lead compounds for drug synthesis and a promise for the future treatment of parasitosis and provide a valid strategy for the development of potent antiparasitic drugs.

Mots clés

  • 2-amino-1
  • 3
  • 4-thiadiazoles
  • antiparasitic activity
  • anti-trypanosomal activity
  • antimalarial activity
  • antitoxoplasmal activity
  • inhibitory concentration
Accès libre

Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

Publié en ligne: 17 Feb 2020
Pages: 291 - 301

Résumé

Abstract

Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy.

Mots clés

  • valproic acid
  • short-chain fatty acids
  • anticancer activities
  • histone deacetylase inhibitors
  • pre-clinical and clinical studies
Accès libre

Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones

Publié en ligne: 17 Feb 2020
Pages: 303 - 324

Résumé

Abstract

Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assuring about 59–93 % yield, low harmful emissions and reagent economy. The structures of the new compounds were elucidated by melting points, TLC characteristics, IR, 1H and 13C NMR spectral data followed by MS data. The purity of the obtained compounds was proven by the corresponding elemental analyses. “Lipinski’s rule of five” parameters were applied for preliminary evaluation of the pharmacokinetic properties of the target molecules. The initial in vitro safety screening for cytotoxicity (on HepG2 cells) and hemocompatibility (hemolysis assay) showed good safety of the new compounds, where ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene)-hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyr-role-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2-hydroxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan--2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4a) were the least toxic. The antioxidant activity in terms of radical scavenging activity (DPPH test) and reducing ability (ABTS) was also evaluated. The antioxidant protective potential of the compounds was next determined in different in vitro cellular-based models, revealing compounds 4d and 3 [ethyl 5-(4-bromophenyl)-1-(1-hydrazineyl-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate] as the most promising compounds, with 4d having better safety profile.

Mots clés

  • pyrrole hydrazones
  • DPPH
  • ABTS
  • cytotoxicity
  • micro-somes
  • oxidative stress
Accès libre

Stability study of thymoquinone, carvacrol and thymol using HPLC-UV and LC-ESI-MS

Publié en ligne: 17 Feb 2020
Pages: 325 - 342

Résumé

Abstract

The aim of this study was to investigate the stability of three major antioxidants of Nigella sativa: thymoquinone (TQ), carvacrol (CR) and thymol (THY), under different stress conditions using HPLC and LC-MS/MS. Forced degradation for each compound was performed under different conditions, including oxidation, hydrolysis, photolysis and thermal decomposition. The results showed that both CR and THY were stable under the studied conditions, whereas TQ was not affected by acidic, basic and oxidative forced conditions but the effect of light and heat was significant. The degradation products of TQ were further investigated and characterized by LC-MS/MS. HPLC-UV method has been fully validated in terms of linearity and range, the limit of detection and quantitation, precision, selectivity, accuracy and robustness. The method was successfully applied to quantitative analysis of the principal antioxidants of Nigella sativa TQ, CR and THY in different phytopharmaceuticals.

Mots clés

  • thymoquinone
  • carvacrol
  • thymol
  • HPLC-UV
  • LC-MS/MS
  • stability
Accès libre

Simultaneous determination of warfarin and 7-hydroxywarfarin in rat plasma by HPLC-FLD

Publié en ligne: 17 Feb 2020
Pages: 343 - 357

Résumé

Abstract

In this study, high-performance liquid chromatography with fluorescence detection (HPLC-FLD) has been used for the first time, for direct determination of warfarin and its major metabolite, 7-hydroxywarfarin, in rat plasma. The simple and sensitive method was developed using Fortis® reversed-phase diphenyl column (150 × 4.6 mm, 3 μm) and a mobile phase composed of phosphate buffer (25 mmol L−1)/methanol/acetonitrile (70:20:10, V/V/V), adjusted to pH 7.4, at a flow rate of 0.8 mL min−1. The diphenyl chemistry of the stationary phase provided a unique selectivity for separating the structurally related aromatic analytes, warfarin and 7-hydroxywarfarin, allowing their successful quantification in the complex plasma matrix. The method was linear over the range 0.01–25 μg mL−1, for warfarin and 7-hydroxywarfarin, and was found to be accurate, precise and selective in accordance with US FDA guidance for bioanalytical method validation. The method was sensitive enough to quantify 0.01 μg mL−1 of warfarin and 7-hydroxywarfarin (LLOQ) using only 100 μL of plasma. The applicability of this method was demonstrated by analyzing samples obtained from rats after oral administration of a single warfarin dose, and studying warfarin and 7-hydroxywarfarin pharmacokinetics.

Mots clés

  • warfarin
  • 7-hydroxywarfarin
  • high-performance liquid chromatography-fluorescence detection
  • rat plasma
  • pharmacokinetics
Accès libre

Advanced flow cell design for in vitro release testing of mucoadhesive buccal films

Publié en ligne: 17 Feb 2020
Pages: 359 - 371

Résumé

Abstract

Films for buccal application are a slowly emerging new platform for drug delivery. There remains a lack of analytical techniques for the determination of in vitro active pharmaceutical ingredient release. The aim here was to develop an alternative method to the commonly used United States Pharmacopoeia (USP) 2 method, based on the flow-through cell. This system extends the release time and enables more detailed sample discrimination according to formulation. It could be used as a tool for in vivo prediction of drug release rates from buccal film formulations. The flow cell contains two chambers separated by a membrane through which the released active pharmaceutical ingredient is measured. Vital system variables and their effects on the release rate of the model active pharmaceutical ingredient are presented for formulations based on sodium alginate polymer. The method reflects the differences between films and is shown to be discriminatory for evaluation of buccal formulations.

Mots clés

  • release rate
  • buccal films
  • hydrostatic pressure
  • flow cell
Accès libre

Simultaneous spectrofluorometric analysis of tablets containing hydrochlorothiazide combined with timolol maleate or amiloride hydrochloride

Publié en ligne: 17 Feb 2020
Pages: 373 - 385

Résumé

Abstract

Green and sensitive spectrofluorometric methods have been developed and validated for the determination of timolol maleate (TML)/hydrochlorothiazide (HCT) and amiloride hydrochloride (AMH)/hydrochlorothiazide in tablets. The proposed spectrofluorometric procedures were found to be linear in the range of 4–12, 5–35 and 0.025–0.2 mg L−1 for HCT, TML and AMH, resp. The excitation and emission wavelengths for HCT, TML and AMH at room temperature were 270 and 375, 295 and 435, 330 and 415 nm, resp. The methods were validated with respect to ICH guidelines. The AMH showed higher sensitivity with lower values of LOD and LOQ values compared to HCT and TML. The proposed methods were applied to two pharmaceutical formulations; the method for HCT and AMH has proven as reliable assaying method, whereas the method for TML, when combined with HCT, is applicable to screening semi-quantitative analyses.

Mots clés

  • hydrochlorothiazide
  • amiloride hydrochloride
  • timolol maleate
  • fixed-dose combinations
  • spectrofluorometry
  • assaying
  • screening
Accès libre

Differential effects of acute and chronic treatment with the flavonoid chrysin on anxiety-like behavior and Fos immunoreactivity in the lateral septal nucleus in rats

Publié en ligne: 17 Feb 2020
Pages: 387 - 397

Résumé

Abstract

The aim of this study was to compare the effects of acute (a single injection) and chronic (21 consecutive days) treatments with chrysin 2, 4, and 8 μmol kg−1 on anxiety-like behavior and Fos immunoreactivity in the lateral septum nucleus (LSN), a structure that is involved in the regulation of anxiety, in male Wistar rats. These effects were compared with the clinically effective anxiolytic diazepam 7 μmol kg−1. The results showed that acute, but not chronic treatment, with 4 μmol kg−1 chrysin exerted anxiolytic- and anti- depressant-like effects with these effects being similar to that of diazepam. Also, none of the above-mentioned treatments did alter Fos immunoreactivity in the LSN, but a tendency towards the reduction of this variable was detected with chrysin 4 μmol kg−1 and diazepam 7 μmol kg−1. Altogether, results suggest that chrysin exerts anxiolytic-like effects, however, it can produce pharmacological tolerance after repeated use, similar to benzodiazepines.

Mots clés

  • chrysin
  • anxiolytic
  • elevated plus maze
  • Fos protein
  • lateral septal nucleus
Accès libre

Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway

Publié en ligne: 17 Feb 2020
Pages: 399 - 409

Résumé

Abstract

Curcumin has been proved to inhibit cell proliferation and induce cell apoptosis in non-small cell lung cancer (NSCLC). However, little is known about antimetastatic effects and molecular mechanisms of curcumin in NSCLC. In this study, we investigated the involvement of miR-206 in curcumin’s anti-invasion and anti-migration in NSCLC. Cell proliferation was determined by MTT assay. Cell migration and invasion were analyzed by wound healing assay and transwell assay. MiRNA-206 expression was detected by real-time PCR. Western blot was used to detect the protein expression of PI3K/AKT/mTOR signaling pathway. Curcumin significantly inhibited migration and invasion in A549 cells, accompanied by significantly elevated miR-206 expression. Overexpression of miR-206 could inhibit migration and invasion of A549 cells, but it could also significantly decrease the phosphorylation levels of mTOR and AKT. The inhibition of miR-206 promoted cell migration, invasion and increased the phosphorylation level of mTOR and AKT. Furthermore, miR-206 mimics improved the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT in A549 cells. On the contrary, MiR-206 inhibitors reversed the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT. In conclusion, curcumin inhibited cell invasion and migration in NSCLC by elevating the expression of miR-206 which further suppressed the activation of the PI3K/AKT/mTOR pathway.

Mots clés

  • curcumin
  • NSCLC
  • microRNAs
  • migration and invasion
Accès libre

Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride

Publié en ligne: 17 Feb 2020
Pages: 411 - 422

Résumé

Abstract

Donepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-β-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer’s disease due to its higher bioavailability and better distribution to brain when compared to oral route.

Mots clés

  • donepezil hydrochloride
  • thermosensitive gel
  • nasal delivery
  • bioavailability
  • brain targeting

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