Enhancement of transdermal delivery of artemisinin using microemulsion vehicle based on ionic liquid and lidocaine ibuprofen.

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/cm3), 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.