In this work, we examined enhanced skin delivery of minoxidil applied in nanoemulsions\nincorporating skin penetration enhancers. Aliquots of fully characterized oil-in-water nanoemulsions\n(1 mL), containing minoxidil (2%) and the skin penetration enhancer oleic acid or eucalyptol as oil\nphases, were applied to full-thickness excised human skin in Franz diffusion cells, while aqueous\nsolutions (1 mL) containing minoxidil were used as controls. Minoxidil in the stratum corneum (SC),\nhair follicles, deeper skin layers, and flux through the skin over 24 h was determined, as well as\nminoxidil solubility in the formulations and in the SC. The nanoemulsions significantly enhanced the\npermeation of minoxidil through skin compared with control solutions. The eucalyptol formulations\n(NE) promoted minoxidil retention in the SC and deeper skin layers more than did the oleic acid\nformulations, while the oleic acid formulations (NO) gave the greatest hair follicle penetration.\nMinoxidil maximum flux enhancement was associated with increases in both minoxidil SC solubility\nand skin diffusivity in both nanoemulsion systems. The mechanism of enhancement appeared to be\ndriven largely by increased diffusivity, rather than increased partitioning into the stratum corneum,\nsupporting the concept of enhanced fluidity and disruption of stratum corneum lipids.
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