Liquid microemulsions appropriate for topical application were obtained by increasing their viscosity through the addition of thickening agents. The present study first assessed the usefulness of ultrasound (US) plus US contrast agent, microbubbles (MBs), in agarose gel for enhancing transdermal drug delivery. The effect of US plus MBs in agarose gel on the penetration of the skin by magnesium ascorbyl phosphate (MAP) was explored both in vitro and in vivo. In the in vitro experiments, the stability of MBs was investigated by examining the penetration of MAP by the model drug, Evans blue, in two media: an agarose phantom and pig skin. The penetration depth in the agarose phantom and pig skin increased by 40% and 195%, respectively, when treated with US plus MBs in 0.1% agarose solution combined with MAP (UMB1), and by 48% and 206%, respectively, when treated with US plus MBs in 0.15% agarose solution and MAP (UMB2). The skin-whitening effects in C57BL/6J mice in the UMB1 and UMB2 groups over a 4-week experimental period were significantly increased by 63% and 70%, respectively, in the fourth week. The findings of this study suggest that the survival of MBs with US is affected by the viscosity of the surrounding medium, and that in mice, treatment with US plus MBs in a suitable agarose gel can increase skin permeability and enhance transdermal MAP delivery.
Keywords: Agarose gel; Magnesium ascorbyl phosphate; Melanin; Microbubbles; Transdermal delivery; Ultrasound.
Copyright © 2015 Elsevier B.V. All rights reserved.