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A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane
The purpose of this work was to investigate the synthetic phospholipid dependence of permeability measured by parallel artificial membrane permeability assay (PAMPA) method. Three phospholipids with hydrophobic groups of different lengths and phosphorylcholine as the hydrophilic group were concisely...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315410/ https://www.ncbi.nlm.nih.gov/pubmed/25647086 http://dx.doi.org/10.1371/journal.pone.0116502 |
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author | Yu, Hui Wang, Qi Sun, Ying Shen, Ming Li, He Duan, Yourong |
author_facet | Yu, Hui Wang, Qi Sun, Ying Shen, Ming Li, He Duan, Yourong |
author_sort | Yu, Hui |
collection | PubMed |
description | The purpose of this work was to investigate the synthetic phospholipid dependence of permeability measured by parallel artificial membrane permeability assay (PAMPA) method. Three phospholipids with hydrophobic groups of different lengths and phosphorylcholine as the hydrophilic group were concisely synthesized. Ten model drug molecules were selected because of their distinct human fraction absorbed (%FA) values and various pK (a) characteristics. In vitro drug permeation experiments were designed to determine the effect of the incubation time (4–20 h), pH gradient (4.6–9.32) and carbon chain length (8, 10, 12) on the drug permeability through the synthetic phospholipid membrane in the PAMPA system. The results showed that intensive and significant synthetic phospholipids dependence of permeability influenced by the length of lipid’s hydrophobic carbon chain. The effective permeability constant (P (e)) of each drug increased rapidly with time, then decreased slightly after reaching the maximum; the pH gradient changed the drug permeability according to the pH-partition hypothesis for drugs with diverse pK (a) values; and longer hydrophobic chains in the synthetic phospholipid membrane improved the drug permeability, as observed for all test drugs at almost all incubation time points. This newly proposed PAMPA model considered the synthetic phospholipid membrane and showed good P (e)-%FA correlation for the passive transport of drugs, making it a helpful supplementary method for PAMPA systems. |
format | Online Article Text |
id | pubmed-4315410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43154102015-02-13 A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane Yu, Hui Wang, Qi Sun, Ying Shen, Ming Li, He Duan, Yourong PLoS One Research Article The purpose of this work was to investigate the synthetic phospholipid dependence of permeability measured by parallel artificial membrane permeability assay (PAMPA) method. Three phospholipids with hydrophobic groups of different lengths and phosphorylcholine as the hydrophilic group were concisely synthesized. Ten model drug molecules were selected because of their distinct human fraction absorbed (%FA) values and various pK (a) characteristics. In vitro drug permeation experiments were designed to determine the effect of the incubation time (4–20 h), pH gradient (4.6–9.32) and carbon chain length (8, 10, 12) on the drug permeability through the synthetic phospholipid membrane in the PAMPA system. The results showed that intensive and significant synthetic phospholipids dependence of permeability influenced by the length of lipid’s hydrophobic carbon chain. The effective permeability constant (P (e)) of each drug increased rapidly with time, then decreased slightly after reaching the maximum; the pH gradient changed the drug permeability according to the pH-partition hypothesis for drugs with diverse pK (a) values; and longer hydrophobic chains in the synthetic phospholipid membrane improved the drug permeability, as observed for all test drugs at almost all incubation time points. This newly proposed PAMPA model considered the synthetic phospholipid membrane and showed good P (e)-%FA correlation for the passive transport of drugs, making it a helpful supplementary method for PAMPA systems. Public Library of Science 2015-02-03 /pmc/articles/PMC4315410/ /pubmed/25647086 http://dx.doi.org/10.1371/journal.pone.0116502 Text en © 2015 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yu, Hui Wang, Qi Sun, Ying Shen, Ming Li, He Duan, Yourong A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane |
title | A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane |
title_full | A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane |
title_fullStr | A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane |
title_full_unstemmed | A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane |
title_short | A New PAMPA Model Proposed on the Basis of a Synthetic Phospholipid Membrane |
title_sort | new pampa model proposed on the basis of a synthetic phospholipid membrane |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315410/ https://www.ncbi.nlm.nih.gov/pubmed/25647086 http://dx.doi.org/10.1371/journal.pone.0116502 |
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