Innovative insight into the mechanism of enantioselective skin permeation for chiral drugs
OBJECTIVES: A profound comprehension of the molecular mechanisms underpinning the enantioselective transdermal permeation of chiral drugs is critical in the design and assessment of transdermal preparations. The primary objective of this study is to investigate the distinct skin permeation behaviors exhibited by enantiomers of non-steroidal anti-inflammatory drugs (NSAIDs) and elucidate the intricate molecular mechanism at play.
METHODS: In vitro and in vivo transdermal permeation studies of chiral NSAIDs were performed using transdermal patch and solution system. Chiral interaction between NSAIDs enantiomers and synthesized chiral ceramide present in the skin was characterized to clarify the different transdermal behaviors.
RESULTS: The S-enantiomers of NSAIDs exhibited higher permeability through the skin than R-enantiomer in vitro (1.5-fold) and in vivo (2.0-fold), which was attributed to a stronger interaction between S-enantiomer and ceramide caused by more favorable spatial conformations. S-enantiomer required lower activation energy (24.4 kJ/mol) and Gibbs energy (43.3 kJ/mol), which was favorable in forming the H-bond with ceramide in the skin, resulting in more permeation.
CONCLUSION: This research furnished an innovative comprehension of the molecular underpinnings governing the enantioselective permeation of drug enantiomers through the skin, fostering the minimization of undesired enantiomer ingestion (distomers) and amplifying therapeutic efficiency.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Expert opinion on drug delivery - 20(2023), 11 vom: 20. Juli, Seite 1643-1656 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yang [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Inflammatory Agents, Non-Steroidal |
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| Anmerkungen: |
Date Completed 22.12.2023 Date Revised 22.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/17425247.2023.2294877 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366028979 |
|---|
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| 245 | 1 | 0 | |a Innovative insight into the mechanism of enantioselective skin permeation for chiral drugs |
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| 500 | |a Date Completed 22.12.2023 | ||
| 500 | |a Date Revised 22.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: A profound comprehension of the molecular mechanisms underpinning the enantioselective transdermal permeation of chiral drugs is critical in the design and assessment of transdermal preparations. The primary objective of this study is to investigate the distinct skin permeation behaviors exhibited by enantiomers of non-steroidal anti-inflammatory drugs (NSAIDs) and elucidate the intricate molecular mechanism at play | ||
| 520 | |a METHODS: In vitro and in vivo transdermal permeation studies of chiral NSAIDs were performed using transdermal patch and solution system. Chiral interaction between NSAIDs enantiomers and synthesized chiral ceramide present in the skin was characterized to clarify the different transdermal behaviors | ||
| 520 | |a RESULTS: The S-enantiomers of NSAIDs exhibited higher permeability through the skin than R-enantiomer in vitro (1.5-fold) and in vivo (2.0-fold), which was attributed to a stronger interaction between S-enantiomer and ceramide caused by more favorable spatial conformations. S-enantiomer required lower activation energy (24.4 kJ/mol) and Gibbs energy (43.3 kJ/mol), which was favorable in forming the H-bond with ceramide in the skin, resulting in more permeation | ||
| 520 | |a CONCLUSION: This research furnished an innovative comprehension of the molecular underpinnings governing the enantioselective permeation of drug enantiomers through the skin, fostering the minimization of undesired enantiomer ingestion (distomers) and amplifying therapeutic efficiency | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chiral | |
| 650 | 4 | |a ceramide | |
| 650 | 4 | |a enantiomers | |
| 650 | 4 | |a enantioselective permeation | |
| 650 | 4 | |a transdermal | |
| 650 | 7 | |a Anti-Inflammatory Agents, Non-Steroidal |2 NLM | |
| 650 | 7 | |a Ceramides |2 NLM | |
| 700 | 1 | |a Liu, Xiaowen |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Guojing |e verfasserin |4 aut | |
| 700 | 1 | |a Gui, Hongzhe |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Jingteng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Mingzhe |e verfasserin |4 aut | |
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