Li Bin, Xiao Ting, Guo Shiqi, Wu Yan, Lai Rongrong, Liu Ziyi, Luo Weixuan, Xu Yuehong
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Int J Pharm. 2023 Apr 25;637:122880. doi: 10.1016/j.ijpharm.2023.122880. Epub 2023 Mar 21.
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.
药物的经皮递送通常受到皮肤低渗透性的限制。本研究的目的是合成基于氧化苦参碱（OMT）和具有不同烷基链长度的脂肪酸（LCFAs）的低共熔溶剂（DESs）作为新型载体，以溶解水不溶性药物并增强经皮渗透。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法（FTIR）、核磁共振（NMR）和分子模拟表明，DESs的形成是由电荷辅助氢键介导的。还研究了包括稳定性、粘度和溶解能力在内的物理化学性质。随后，评估了三种稳定的DESs对药物释放和皮肤渗透性的影响。结果表明，QUE在DESs中溶解良好，并呈现出不同的缓释行为。同时，DESs增强了OMT和QUE的皮肤渗透，这受到LCFAs烷基链长度的影响，而由月桂酸（LA）组成的DES表现出最高的增强效果。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之间的一致性。此外，用DESs处理的HaCaT细胞显示出高细胞活力，表明它们具有良好的皮肤安全性。综上所述，OMT-LCFA DESs将是一种有前途的经皮给药渗透促进剂，这也为新型DESs的设计提供了指导。
