scholarly journals Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Classified Drugs

2020 ◽  
Author(s):  
Leonardo de Souza Teixeira ◽  
Tatiana Vila Chagas ◽  
Antonio Alonso ◽  
Maria Isabel Gonzalez ◽  
Marival Bermejo ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Oral Drug ◽  
Resonance Spectroscopy ◽  
Artificial Membrane ◽  
Apparent Permeability ◽  
Paramagnetic Resonance ◽  
Franz Cell ◽  
Fda Guidance ◽  
Permeability Assay

A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-Bampa) was validated using Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-Bampa were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for the 14 BCS class I-IV drugs cited in the FDA guidance (including other drugs as acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-Bampa. Apparent permeability (Papp) was compared to literature fraction dose absorbed in humans (Fa%). Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-Bampa performance. Mannitol and metoprolol Papp values across Franz-Bampa were lower (3.20 x 10-7 and 1.61 x 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 x 10-5 and 2.55 x 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed similar log linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-Bampa method for use during drug discovery process.

scholarly journals Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 988
Author(s):  
Leonardo de Souza Teixeira ◽  
Tatiana Vila Chagas ◽  
Antonio Alonso ◽  
Isabel Gonzalez-Alvarez ◽  
Marival Bermejo ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Oral Drug ◽  
Resonance Spectroscopy ◽  
Artificial Membrane ◽  
Apparent Permeability ◽  
Franz Cell ◽  
Bcs Model ◽  
Fda Guidance ◽  
Permeability Assay

A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz–PAMPA Pampa) was validated using a Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz–PAMPA were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for eight Biopharmaceutic Classification System (BCS) model drugs cited in the FDA guidance and another six drugs (acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz–PAMPA. Apparent permeability (Papp) Franz–PAMPA values were correlated with fraction of dose absorbed in humans (Fa%) from the literature. Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz–PAMPA performance. Mannitol and metoprolol Papp values across Franz–PAMPA were lower (3.20 × 10−7 and 1.61 × 10−5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 × 10−5 and 2.55 × 10−5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed acceptable log-linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz–PAMPA method for use during the drug discovery process.

scholarly journals Tauroursodeoxycholic Acid (TUDCA)—Lipid Interactions and Antioxidant Properties of TUDCA Studied in Model of Photoreceptor Membranes

Membranes ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 327
Author(s):  
Michał J. Sabat ◽  
Anna M. Wiśniewska-Becker ◽  
Michał Markiewicz ◽  
Katarzyna M. Marzec ◽  
Jakub Dybas ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Plasma Membranes ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Protective Action ◽  
Antioxidant Properties ◽  
Model Membranes ◽  
Dynamics Simulation ◽  
Resonance Spectroscopy ◽  
Paramagnetic Resonance ◽  
Tauroursodeoxycholic Acid

Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid containing taurine conjugated with the ursodeoxycholic acid (UDCA), has been known and used from ancient times as a therapeutic compound in traditional Chinese medicine. TUDCA has recently been gaining significant interest as a neuroprotective agent, also exploited in the visual disorders. Among several mechanisms of TUDCA’s protective action, its antioxidant activity and stabilizing effect on mitochondrial and plasma membranes are considered. In this work we investigated antioxidant activity of TUDCA and its impact on structural properties of model membranes of different composition using electron paramagnetic resonance spectroscopy and the spin labeling technique. Localization of TUDCA molecules in a pure POPC bilayer has been studied using a molecular dynamics simulation (MD). The obtained results indicate that TUDCA is not an efficient singlet oxygen (1O2 (1Δg)) quencher, and the determined rate constant of its interaction with 1O2 (1Δg) is only 1.9 × 105 M−1s−1. However, in lipid oxidation process induced by a Fenton reaction, TUDCA reveals substantial antioxidant activity significantly decreasing the rate of oxygen consumption in the system studied. In addition, TUDCA induces slight, but noticeable changes in the polarity and fluidity of the investigated model membranes. The results of performed MD simulation correspond very well with the experimental results.

scholarly journals Ambient base-free glycerol oxidation over bimetallic PdFe/SiO2 by in situ generated active oxygen species

2021 ◽  
Author(s):  
Ricci Underhill ◽  
Mark Douthwaite ◽  
Richard J. Lewis ◽  
Peter J. Miedziak ◽  
Robert D. Armstrong ◽  
...  
Keyword(s):  
Heterogeneous Catalysts ◽  
Bimetallic Catalyst ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Active Oxygen Species ◽  
Catalytic Performance ◽  
Resonance Spectroscopy ◽  
Oxygen Species ◽  
Paramagnetic Resonance ◽  
Temperature Oxidation

AbstractLow temperature oxidation of alcohols over heterogeneous catalysts is exceptionally challenging, particularly under neutral conditions. Herein, we report on an efficient, base-free method to oxidise glycerol over a 0.5%Pd-0.5%Fe/SiO2 catalyst at ambient temperature in the presence of gaseous H2 and O2. The exceptional catalytic performance was attributed to the in situ formation of highly reactive surface-bound oxygenated species, which promote the dehydrogenation on the alcohol. The PdFe bimetallic catalyst was determined to be significantly more active than corresponding monometallic analogues, highlighting the important role both metals have in this oxidative transformation. Fe leaching was confirmed to occur over the course of the reaction but sequestering experiments, involving the addition of bare carbon to the reactions, confirmed that the reaction was predominantly heterogeneous in nature. Investigations with electron paramagnetic resonance spectroscopy suggested that the reactivity in the early stages was mediated by surface-bound reactive oxygen species; no homogeneous radical species were observed in solution. This theory was further evidenced by a direct H2O2 synthesis study, which confirmed that the presence of Fe in the bimetallic catalyst neither improved the synthesis of H2O2 nor promoted its decomposition over the PdFe/SiO2 catalyst.

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