Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Innovation Academy for Green Manufacture, Chinese Academy of Sciences, No. 1 Beierjie, Zhongguancun, Haidian District, Beijing, 100190, PR China; Sino-Danish College, University of Chinese Academy of Sciences, Yanqihu Campus, No. 380 Huaibeizhuang, Huairou District, Beijing, 101408, PR China.
Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Innovation Academy for Green Manufacture, Chinese Academy of Sciences, No. 1 Beierjie, Zhongguancun, Haidian District, Beijing, 100190, PR China.
Colloids Surf B Biointerfaces. 2020 May;189:110886. doi: 10.1016/j.colsurfb.2020.110886. Epub 2020 Feb 19.
A microemulsion system based on ionic liquid (IL) and deep eutectic compound was proposed to improve the transdermal delivery of artemisinin. Deep eutectic lidocaine ibuprofen (Lid·Ibu) was selected as the oil phase, and the imidazolium ionic liquid, 1-hydroxyethyl-3-methylimidazolium chloride ([HOEmim]Cl), was incorporated into the aqueous phase as a transdermal enhancer. The ingredients for the microemulsion in this study were selected, and their ratios were optimized. The optimal microemulsion carrier was composed of 45 wt% of water phase, 45 wt% surfactant phase (containing Tween-80, Span-20, and ethanol (co-surfactant) with the weight ratio of 1:1:1), and 10 wt% Lid·Ibu as the oil phase with artemisinin loading of 1.0 wt% (all the ratios were based on the total weight of microemulsion). Physical properties of this microemulsion, including particle size (41.95 ± 0.85 nm), viscosity (26.65 ± 0.13 mPa·s) and density (1.02 g/cm), were measured. In-vitro transdermal assay showed a remarkable enhancement of artemisinin transport through the skin, with the permeation flux being 3-fold of the value for isopropyl myristate system in 6 h. The impact of IL-based microemulsion (ILME) on stratum corneum (SC) was investigated by DSC, ATR-FTIR and AFM, which unveiled that the ILME possesses the ability of reducing the SC barrier by disrupting the regular arrangement of keratin, resulting in enhancement of transdermal delivery of artemisinin. This current work suggested that the microemulsion proposed here had an excellent capability to promote the transdermal delivery of artemisinin, which might also be a promising vehicle for the skin delivery of other hydrophobic natural drugs.
基于离子液体（IL）和深共晶化合物的微乳液系统被提出以改善青蒿素的透皮传递。深共晶利多卡因布洛芬（Lid·Ibu）被选为油相，而咪唑离子液体 1-羟乙基-3-甲基咪唑氯化物 ([HOEmim]Cl) 被掺入水相作为透皮增强剂。本研究中微乳液的成分被选择，其比例被优化。最佳微乳液载体由 45wt%水相、45wt%表面活性剂相（包含 Tween-80、Span-20 和乙醇（共表面活性剂），重量比为 1:1:1）和 10wt% Lid·Ibu 组成油相，青蒿素负载量为 1.0wt%（所有比例均基于微乳液的总重量）。该微乳液的物理性质，包括粒径（41.95±0.85nm）、粘度（26.65±0.13mPa·s）和密度（1.02g/cm）进行了测量。体外透皮试验表明，青蒿素通过皮肤的传递得到了显著增强，6 小时内的渗透通量是肉豆蔻异丙酯系统的 3 倍。通过 DSC、ATR-FTIR 和 AFM 研究了基于 IL 的微乳液（ILME）对角质层（SC）的影响，结果表明 ILME 具有通过破坏角蛋白的规则排列来降低 SC 屏障的能力，从而增强青蒿素的透皮传递。本工作表明，所提出的微乳液具有优异的促进青蒿素透皮传递的能力，也可能是其他疏水性天然药物经皮传递的有前途的载体。
