Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Expert Opin Drug Deliv. 2023 Jul-Dec;20(11):1643-1656. doi: 10.1080/17425247.2023.2294877. Epub 2023 Dec 20.
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.
and 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.
The S-enantiomers of NSAIDs exhibited higher permeability through the skin than R-enantiomer (1.5-fold) and (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.
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.
深入理解手性药物经皮渗透的分子机制对于经皮制剂的设计和评估至关重要。本研究的主要目的是研究非甾体抗炎药（NSAIDs）对映异构体的不同皮肤渗透行为，并阐明其中涉及的复杂分子机制。
采用经皮贴剂和溶液系统对手性 NSAIDs 进行经皮渗透研究。对 NSAIDs 对映异构体与皮肤中合成的手性神经酰胺之间的手性相互作用进行了表征，以阐明不同的经皮行为。
与 R-对映异构体相比，S-对映异构体的 NSAIDs 透过皮肤的渗透性更高（1.5 倍和 2.0 倍），这归因于 S-对映异构体与神经酰胺之间更强的相互作用，这是由于其更有利的空间构象所致。S-对映异构体需要更低的活化能（24.4 kJ/mol）和吉布斯能（43.3 kJ/mol），这有利于在皮肤中与神经酰胺形成氢键，从而增加渗透。
本研究为药物对映异构体通过皮肤的手性渗透的分子基础提供了新的认识，有助于减少不必要的对映异构体摄入（差向异构体）并提高治疗效率。
