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Innovative insight into the mechanism of enantioselective skin permeation for chiral drugs.
Zhang, Yang; Liu, Xiaowen; Yu, Guojing; Gui, Hongzhe; Chi, Jingteng; Liu, Shuhan; Fang, Liang; Liu, Mingzhe.
Afiliación
  • Zhang Y; Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Liu X; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Yu G; Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Gui H; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Chi J; Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Liu S; Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Fang L; Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
  • Liu M; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Expert Opin Drug Deliv ; 20(11): 1643-1656, 2023.
Article en En | MEDLINE | ID: mdl-38112192
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Absorción Cutánea Idioma: En Revista: Expert Opin Drug Deliv Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Absorción Cutánea Idioma: En Revista: Expert Opin Drug Deliv Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido