School of Engineering and Applied Sciences, 52 Oxford St, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, 52 Oxford St, Cambridge, MA 02138, USA.
School of Engineering and Applied Sciences, 52 Oxford St, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, 52 Oxford St, Cambridge, MA 02138, USA.
J Control Release. 2019 Oct;311-312:162-169. doi: 10.1016/j.jconrel.2019.08.029. Epub 2019 Aug 26.
Transdermal delivery of large hydrophilic molecules is a long-standing challenge owing to the strong diffusive barrier properties of the skin. Using choline and geranic acid (CAGE) based ionic liquid (IL) as a delivery technology, we report a significant improvement of transdermal transport of dextrans of various molecular weights up to 150 kDa. In addition, it is the first time that we show CAGE decreased the size-dependence of transport and thus can be applied to a broad range of solutes. At the molecular scale, we conducted Fourier Transform Infrared (FTIR) spectroscopy studies which showed lipid extraction in the skin due to CAGE. Based on these experimental observations, we built a novel theoretical model that elucidates how CAGE-induced skin structural changes result in faster macromolecular diffusion for enhanced permeability. The fundamental understanding gained from this study demonstrates the potential of ionic liquids as an effective and noninvasive transdermal drug delivery method.
由于皮肤具有很强的扩散屏障特性，因此将大亲水性分子经皮递送给是一个长期存在的挑战。本研究采用胆碱和香叶基酸（CAGE）为基础的离子液体（IL）作为递药技术，报告了对各种分子量的葡聚糖（高达 150 kDa）的经皮转运有显著改善。此外，这是首次表明 CAGE 降低了转运的尺寸依赖性，因此可以应用于广泛的溶质。在分子水平上，我们进行了傅里叶变换红外（FTIR）光谱研究，结果表明 CAGE 导致了皮肤中的脂质提取。基于这些实验观察，我们建立了一个新的理论模型，阐明了 CAGE 如何引起皮肤结构变化，从而导致大分子扩散更快，渗透性增强。这项研究的基本认识表明，离子液体作为一种有效和非侵入性的经皮药物传递方法具有潜力。
