Understanding the transport of drugs across biomimetic barriers of various phospholipid compositions using a combined experimental and computational approach.
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| Title: | Understanding the transport of drugs across biomimetic barriers of various phospholipid compositions using a combined experimental and computational approach. |
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| Authors: | Kabedev, Aleksei1 (AUTHOR), Tønning, Mikkel Højmark1,2 (AUTHOR), Teleki, Alexandra3 (AUTHOR), Bauer-Brandl, Annette2 (AUTHOR), Jacobsen, Ann-Christin1,2,4 (AUTHOR) ajacobsen@pharmazie.uni-kiel.de |
| Source: | Colloids & Surfaces B: Biointerfaces. Sep2025, Vol. 253, pN.PAG-N.PAG. 1p. |
| Subjects: | Cell membranes, Artificial membranes, Phosphatidylglycerol, Biological systems, Lecithin |
| Abstract: | Permeapad® is an artificial biomimetic barrier for in vitro permeation experiments, which has an intricate nano- and microstructure consisting of two cellulose hydrate sheets enclosing a layer of phospholipids forming multiple, multilamellar vesicles in contact with the assay medium. Due to this structure, transport across this barrier can be regarded as complex deserving further attention. Until now, only Permeapad® with phosphatidylcholine, the most abundant phospholipid in cell membranes, has been described in literature. However, from biological systems and other artificial barriers, it is known that permeation properties can vary with phospholipid composition. This study presents a combination of experimental and computational techniques to study and explain the transport of molecules across the Permeapad® barrier. For this, we investigated Permeapad® variants with other phospholipid compositions including phosphatidylethanolamine, the second most abundant phospholipid in cell membranes, and phosphatidylglycerol, representing a phospholipid with a negatively charged headgroup by measuring the permeability of three drugs, metoprolol (a weak base), naproxen (a weak acid) and hydrocortisone (a non-ionizable drug). Phospholipid composition only affected the permeability of metoprolol significantly. We used molecular dynamics simulations to understand the underlying mechanisms of the permeability differences extracting several descriptors of membrane properties and predicting permeability. Surprisingly, an almost inverse relationship between experimental and computational permeability was observed. Permeapad®'s highly compartmentalized structure was hypothesized to cause this observation. This study offers a deeper understanding of the functionality of the Permeapad® barrier. • Permeapad®'s phospholipid composition affected metoprolol's permeability. • Naproxen's and hydrocortisone's permeability were not affected. • MD simulations yielded properties of membranes with PC, PE, and PG. • Experimental and computational permeability were surprisingly inversely related. • Pathways to cross Permeapad® are hypothesized based on permeation and MD results. [ABSTRACT FROM AUTHOR] |
| Copyright of Colloids & Surfaces B: Biointerfaces is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 185807241 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Understanding the transport of drugs across biomimetic barriers of various phospholipid compositions using a combined experimental and computational approach. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Kabedev%2C+Aleksei%22">Kabedev, Aleksei</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tønning%2C+Mikkel+Højmark%22">Tønning, Mikkel Højmark</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Teleki%2C+Alexandra%22">Teleki, Alexandra</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bauer-Brandl%2C+Annette%22">Bauer-Brandl, Annette</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jacobsen%2C+Ann-Christin%22">Jacobsen, Ann-Christin</searchLink><relatesTo>1,2,4</relatesTo> (AUTHOR)<i> ajacobsen@pharmazie.uni-kiel.de</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Colloids+%26+Surfaces+B%3A+Biointerfaces%22">Colloids & Surfaces B: Biointerfaces</searchLink>. Sep2025, Vol. 253, pN.PAG-N.PAG. 1p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cell+membranes%22">Cell membranes</searchLink><br /><searchLink fieldCode="DE" term="%22Artificial+membranes%22">Artificial membranes</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphatidylglycerol%22">Phosphatidylglycerol</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+systems%22">Biological systems</searchLink><br /><searchLink fieldCode="DE" term="%22Lecithin%22">Lecithin</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Permeapad® is an artificial biomimetic barrier for in vitro permeation experiments, which has an intricate nano- and microstructure consisting of two cellulose hydrate sheets enclosing a layer of phospholipids forming multiple, multilamellar vesicles in contact with the assay medium. Due to this structure, transport across this barrier can be regarded as complex deserving further attention. Until now, only Permeapad® with phosphatidylcholine, the most abundant phospholipid in cell membranes, has been described in literature. However, from biological systems and other artificial barriers, it is known that permeation properties can vary with phospholipid composition. This study presents a combination of experimental and computational techniques to study and explain the transport of molecules across the Permeapad® barrier. For this, we investigated Permeapad® variants with other phospholipid compositions including phosphatidylethanolamine, the second most abundant phospholipid in cell membranes, and phosphatidylglycerol, representing a phospholipid with a negatively charged headgroup by measuring the permeability of three drugs, metoprolol (a weak base), naproxen (a weak acid) and hydrocortisone (a non-ionizable drug). Phospholipid composition only affected the permeability of metoprolol significantly. We used molecular dynamics simulations to understand the underlying mechanisms of the permeability differences extracting several descriptors of membrane properties and predicting permeability. Surprisingly, an almost inverse relationship between experimental and computational permeability was observed. Permeapad®'s highly compartmentalized structure was hypothesized to cause this observation. This study offers a deeper understanding of the functionality of the Permeapad® barrier. • Permeapad®'s phospholipid composition affected metoprolol's permeability. • Naproxen's and hydrocortisone's permeability were not affected. • MD simulations yielded properties of membranes with PC, PE, and PG. • Experimental and computational permeability were surprisingly inversely related. • Pathways to cross Permeapad® are hypothesized based on permeation and MD results. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Colloids & Surfaces B: Biointerfaces is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.colsurfb.2025.114706 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 1 StartPage: N.PAG Subjects: – SubjectFull: Cell membranes Type: general – SubjectFull: Artificial membranes Type: general – SubjectFull: Phosphatidylglycerol Type: general – SubjectFull: Biological systems Type: general – SubjectFull: Lecithin Type: general Titles: – TitleFull: Understanding the transport of drugs across biomimetic barriers of various phospholipid compositions using a combined experimental and computational approach. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Kabedev, Aleksei – PersonEntity: Name: NameFull: Tønning, Mikkel Højmark – PersonEntity: Name: NameFull: Teleki, Alexandra – PersonEntity: Name: NameFull: Bauer-Brandl, Annette – PersonEntity: Name: NameFull: Jacobsen, Ann-Christin IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 09 Text: Sep2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 09277765 Numbering: – Type: volume Value: 253 Titles: – TitleFull: Colloids & Surfaces B: Biointerfaces Type: main |
| ResultId | 1 |
