Hydrophilic drugs are difficult to penetrate the stratum corneum (SC) of the skin. Microemulsions (MEs) can improve drug penetration through the skin, but the relationship between the MEs structures and their skin permeabilities is still unknown. In this study, we focused on the ME dispersed in the oil phase containing deep eutectic solvent (DES). DESs consist of hydrogen-bond acceptors and appreciate hydrogen-bond donors and form a eutectic with a melting point much lower than each component. Since the SC has a hydrophobic property, hydrophobic DESs could be used as a potential solvent for a drug penetration enhancer through the SC.<br/>First, we prepared hydrophobic DESs, composed of l-menthol and myristic acid, and then investigated the interaction between the SC and the mixed solvent of hydrophobic DESs and isopropyl myristate (IPM) with X-ray scattering. Terpene compounds, including l-menthol, have been widely used as skin penetration enhancers, and IPM is often used as the oil phase of MEs. The results showed that DES and IPM preferentially disrupted long and short lamellar structure among the SC lipid lamellar structures, respectively. Moreover, we found that DES disrupted the lamellar more than IPM.<br/>Subsequently, the structural characterization of the MEs and their skin penetration were evaluated. MEs were prepared by adding Tween-80, Span-20, and water to the different ratios of DES and IPM. The weight ratio of surfactants/water/solvent was fixed at 20/4/76. The SAXS profiles of the MEs showed that the structural change occurred from a sphere to a cylinder with increasing DES ratio, and the further addition of DES to the solvent caused the formation of the aggregates (Fig.1a). Additionally, we found that adding DES to IPM improved ME penetration through the skin with increasing DES up to DES/IPM=1/1 (wt/wt) because DES disrupted more SC lipid lamellar than IPM (Fig.1b). However, further addition of DES reduced the skin penetration due to the formation of the ME aggregates.

Characterization of microemulsions dispersed in l-menthol based hydrophobic deep eutectic solvent as potential carriers for transdermal drug delivery

ACS Fall 2021

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