Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers
The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/223 |
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| author | Michele Verboni Diego Romano Perinelli Carol Yingshan Qiu Mattia Tiboni Annalisa Aluigi Simone Lucarini Jenny K. W. Lam Andrea Duranti |
| author_facet | Michele Verboni Diego Romano Perinelli Carol Yingshan Qiu Mattia Tiboni Annalisa Aluigi Simone Lucarini Jenny K. W. Lam Andrea Duranti |
| author_sort | Michele Verboni |
| collection | DOAJ |
| description | The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological profile. A valid alternative is represented by the class of sugar-based ester surfactants. In this study, sucrose and lactose alkyl aromatic and aromatic ester derivatives have been synthesized with the aim to characterize them in terms of their physicochemical properties, structure–property relationship, and cytotoxicity, and to test their ability as permeability enhancer agents across Calu-3 cells. All of the tested surfactants showed no remarkable cytotoxic effect on Calu-3 cells when applied both below and above their critical micelle concentration. Among the explored molecules, lactose <i>p</i>-biphenyl benzoate (URB1420) and sucrose <i>p</i>-phenyl benzoate (URB1481) cause a reversible ~30% decrease in transepithelial electrical resistance (TEER) with the respect to the basal value. The obtained result matches with the increased in vitro permeability coefficients (P<sub>app</sub>) calculated for FTIC-dextran across Calu-3 cells in the presence of 4 mM solutions of these surfactants. Overall, this study proposes sucrose- and lactose-based alkyl aromatic and aromatic ester surfactants as novel potential and safe permeation enhancers for pharmaceutical applications. |
| first_indexed | 2024-03-11T08:17:36Z |
| format | Article |
| id | doaj.art-1a88ca53f78242048630ed75607cc1ce |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:17:36Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-1a88ca53f78242048630ed75607cc1ce2023-11-16T22:36:41ZengMDPI AGPharmaceuticals1424-82472023-02-0116222310.3390/ph16020223Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability EnhancersMichele Verboni0Diego Romano Perinelli1Carol Yingshan Qiu2Mattia Tiboni3Annalisa Aluigi4Simone Lucarini5Jenny K. W. Lam6Andrea Duranti7Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, PU, ItalySchool of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, MC, ItalyDepartment of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, ChinaDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, PU, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, PU, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, PU, ItalyDepartment of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, ChinaDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, PU, ItalyThe delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological profile. A valid alternative is represented by the class of sugar-based ester surfactants. In this study, sucrose and lactose alkyl aromatic and aromatic ester derivatives have been synthesized with the aim to characterize them in terms of their physicochemical properties, structure–property relationship, and cytotoxicity, and to test their ability as permeability enhancer agents across Calu-3 cells. All of the tested surfactants showed no remarkable cytotoxic effect on Calu-3 cells when applied both below and above their critical micelle concentration. Among the explored molecules, lactose <i>p</i>-biphenyl benzoate (URB1420) and sucrose <i>p</i>-phenyl benzoate (URB1481) cause a reversible ~30% decrease in transepithelial electrical resistance (TEER) with the respect to the basal value. The obtained result matches with the increased in vitro permeability coefficients (P<sub>app</sub>) calculated for FTIC-dextran across Calu-3 cells in the presence of 4 mM solutions of these surfactants. Overall, this study proposes sucrose- and lactose-based alkyl aromatic and aromatic ester surfactants as novel potential and safe permeation enhancers for pharmaceutical applications.https://www.mdpi.com/1424-8247/16/2/223glycolipidssucrose monoesterslactose monoesterssugar-based surfactantsbiocompatibility studiespermeability enhancers |
| spellingShingle | Michele Verboni Diego Romano Perinelli Carol Yingshan Qiu Mattia Tiboni Annalisa Aluigi Simone Lucarini Jenny K. W. Lam Andrea Duranti Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers Pharmaceuticals glycolipids sucrose monoesters lactose monoesters sugar-based surfactants biocompatibility studies permeability enhancers |
| title | Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers |
| title_full | Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers |
| title_fullStr | Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers |
| title_full_unstemmed | Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers |
| title_short | Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers |
| title_sort | synthesis and properties of sucrose and lactose based aromatic ester surfactants as potential drugs permeability enhancers |
| topic | glycolipids sucrose monoesters lactose monoesters sugar-based surfactants biocompatibility studies permeability enhancers |
| url | https://www.mdpi.com/1424-8247/16/2/223 |
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