Oxymatrine-fatty acid deep eutectic solvents as novel penetration enhancers for transdermal drug delivery: formation mechanism and enhancing effect.
Oxymatrine-fatty acid deep eutectic solvents as novel penetration enhancers for transdermal drug delivery: formation mechanism and enhancing effect.
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DOI：
10.1016/j.ijpharm.2023.122880
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发表时间：
2023-03
影响因子：
5.8
通讯作者：
Bin Li;Ting Xiao;Shiqi Guo;Yan Wu;Rongrong Lai;Ziyi Liu;W. Luo;Yue-hong Xu
中科院分区：
文献类型：
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作者：
Bin Li;Ting Xiao;Shiqi Guo;Yan Wu;Rongrong Lai;Ziyi Liu;W. Luo;Yue-hong Xu
经皮给药通常受到皮肤渗透性低的限制。本研究以氧化苦参碱（OMT）和不同烷基链长的脂肪酸（LCFAs）为载体，合成深度共晶溶剂（DESs），以实现水不溶性药物的溶解和经皮渗透。选择槲皮素（QUE）作为模型药物。结合差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）、核磁共振（NMR）和分子模拟，证实了DESs的形成是由电荷辅助氢键介导的。研究了其理化性质，包括稳定性、粘度和增溶能力。随后，评估了三种稳定的DESs对药物释放和皮肤通透性的影响。结果表明，QUE在DESs中具有良好的溶解性和不同的缓释特性。同时，DESs增强OMT和QUE的透皮作用受LCFAs的烷基链长度的影响，而由月桂酸（LA）组成的DES增强作用最大。FTIR、DSC和分子对接进一步证明了微观分子机制与宏观渗透行为的一致性。此外，经DESs处理的HaCaT细胞显示出较高的细胞活力，表明其具有良好的皮肤安全性。综上所述，OMT-LCFA DESs可能是一种很有前景的经皮给药渗透增强剂，这也为新型DESs的设计提供了指导。
Transdermal delivery of drugs is commonly limited by low skin permeability. The aim of the study was to synthesize deep eutectic solvents (DESs) based on oxymatrine (OMT) and fatty acids with various alkyl chain lengths (LCFAs) as novel vehicles, to solubilize the water-insoluble drug and enhance percutaneous penetration. Quercetin (QUE) was selected as a model drug. Combining differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular simulations demonstrated that the formation of DESs was mediated by charge-assisted hydrogen bonding. Physicochemical properties including stability, viscosity, and solubilization capacity were also studied. Subsequently, the effect of three stable DESs on drug release and skin permeability was evaluated. The results showed that QUE was solubilized well and presented a different sustained release behavior in DESs. Meanwhile, DESs enhanced the skin permeation of OMT and QUE, which was influenced by alkyl chain lengths of LCFAs, whereas DES consisting of lauric acid (LA) exhibited the highest enhancing effect. FTIR, DSC, and molecular docking further demonstrated consistency between micro molecular mechanism and macro penetration behavior. Additionally, HaCaT cells treated with DESs showed high cell viability, suggesting their good skin safety. Taken together, OMT-LCFA DESs would be a promising penetration enhancer for transdermal drug delivery, which also provides guidance for the design of new DESs.