Abd Eman, Benson Heather A E, Roberts Michael S, Grice Jeffrey E
Therapeutics Research Centre, School of Medicine, Translational Research Institute, University of Queensland, Brisbane 4102, Australia.
Curtin Health Innovation Research Institute, School of Pharmacy, Curtin University, Perth 6845, Australia.
Pharmaceutics. 2018 Jan 25;10(1):19. doi: 10.3390/pharmaceutics10010019.
In this work, we examined enhanced skin delivery of minoxidil applied in nanoemulsions incorporating skin penetration enhancers. Aliquots of fully characterized oil-in-water nanoemulsions (1 mL), containing minoxidil (2%) and the skin penetration enhancer oleic acid or eucalyptol as oil phases, were applied to full-thickness excised human skin in Franz diffusion cells, while aqueous solutions (1 mL) containing minoxidil were used as controls. Minoxidil in the stratum corneum (SC), hair follicles, deeper skin layers, and flux through the skin over 24 h was determined, as well as minoxidil solubility in the formulations and in the SC. The nanoemulsions significantly enhanced the permeation of minoxidil through skin compared with control solutions. The eucalyptol formulations (NE) promoted minoxidil retention in the SC and deeper skin layers more than did the oleic acid formulations, while the oleic acid formulations (NO) gave the greatest hair follicle penetration. Minoxidil maximum flux enhancement was associated with increases in both minoxidil SC solubility and skin diffusivity in both nanoemulsion systems. The mechanism of enhancement appeared to be driven largely by increased diffusivity, rather than increased partitioning into the stratum corneum, supporting the concept of enhanced fluidity and disruption of stratum corneum lipids.
在本研究中，我们考察了在含有皮肤渗透促进剂的纳米乳剂中应用的米诺地尔的皮肤递送增强情况。将充分表征的水包油纳米乳剂（1 mL）的等分试样，其中含有米诺地尔（2%）以及作为油相的皮肤渗透促进剂油酸或桉叶油素，应用于Franz扩散池中全层切除的人皮肤，同时将含有米诺地尔的水溶液（1 mL）用作对照。测定了角质层（SC）、毛囊、更深层皮肤中的米诺地尔以及24小时内通过皮肤的通量，以及米诺地尔在制剂和SC中的溶解度。与对照溶液相比，纳米乳剂显著增强了米诺地尔透过皮肤的渗透。桉叶油素制剂（NE）比油酸制剂更能促进米诺地尔在SC和更深层皮肤中的保留，而油酸制剂（NO）使毛囊渗透最大。在两个纳米乳剂体系中，米诺地尔的最大通量增强与米诺地尔在SC中的溶解度和皮肤扩散系数的增加有关。增强机制似乎主要由扩散系数的增加驱动，而不是增加在角质层中的分配，这支持了角质层脂质流动性增强和破坏的概念。
