Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs
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 permeabilit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/10/988 |
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| author | Leonardo de Souza Teixeira Tatiana Vila Chagas Antonio Alonso Isabel Gonzalez-Alvarez Marival Bermejo James Polli Kênnia Rocha Rezende |
| author_facet | Leonardo de Souza Teixeira Tatiana Vila Chagas Antonio Alonso Isabel Gonzalez-Alvarez Marival Bermejo James Polli Kênnia Rocha Rezende |
| author_sort | Leonardo de Souza Teixeira |
| collection | DOAJ |
| description | 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<sup>−7</sup> and 1.61 × 10<sup>−5</sup> cm/s, respectively) than those obtained across non-impregnated membrane (2.27 × 10<sup>−5</sup> and 2.55 × 10<sup>−5</sup> cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed acceptable log-linear correlation (R<sup>2</sup> = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R<sup>2</sup> = 0.805). Data support the validation of the Franz–PAMPA method for use during the drug discovery process. |
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| format | Article |
| id | doaj.art-7a9e7e6bee9c4304aa23dbe939816449 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T15:30:38Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7a9e7e6bee9c4304aa23dbe9398164492023-11-20T17:41:47ZengMDPI AGPharmaceutics1999-49232020-10-01121098810.3390/pharmaceutics12100988Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model DrugsLeonardo de Souza Teixeira0Tatiana Vila Chagas1Antonio Alonso2Isabel Gonzalez-Alvarez3Marival Bermejo4James Polli5Kênnia Rocha Rezende6Institute of Pharmaceutical Sciences, Goiânia, Goiás 74175-100, BrazilLaboratory of Biopharmacy and Pharmacokinetics (BioPK), Faculty of Pharmacy, Federal University of Goiás, Goiânia, Goiás 74175-100, BrazilInstitute of Physics, Federal University of Goiás, Goiânia, Goiás 74175-100, BrazilDepartment of Engineering, Pharmacy Section, Miguel Hernandez University, 03550 Alicante, SpainDepartment of Engineering, Pharmacy Section, Miguel Hernandez University, 03550 Alicante, SpainFaculty of Pharmacy, University of Maryland, Baltimore, MD 21021, USALaboratory of Biopharmacy and Pharmacokinetics (BioPK), Faculty of Pharmacy, Federal University of Goiás, Goiânia, Goiás 74175-100, BrazilA 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<sup>−7</sup> and 1.61 × 10<sup>−5</sup> cm/s, respectively) than those obtained across non-impregnated membrane (2.27 × 10<sup>−5</sup> and 2.55 × 10<sup>−5</sup> cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed acceptable log-linear correlation (R<sup>2</sup> = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R<sup>2</sup> = 0.805). Data support the validation of the Franz–PAMPA method for use during the drug discovery process.https://www.mdpi.com/1999-4923/12/10/988Franz–PAMPABCS drugsbiomimetic membraneFranz cellpassive drug transport |
| spellingShingle | Leonardo de Souza Teixeira Tatiana Vila Chagas Antonio Alonso Isabel Gonzalez-Alvarez Marival Bermejo James Polli Kênnia Rocha Rezende Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs Pharmaceutics Franz–PAMPA BCS drugs biomimetic membrane Franz cell passive drug transport |
| title | Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs |
| title_full | Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs |
| title_fullStr | Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs |
| title_full_unstemmed | Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs |
| title_short | Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs |
| title_sort | biomimetic artificial membrane permeability assay over franz cell apparatus using bcs model drugs |
| topic | Franz–PAMPA BCS drugs biomimetic membrane Franz cell passive drug transport |
| url | https://www.mdpi.com/1999-4923/12/10/988 |
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