Sintov Amnon C, Greenberg Igor
Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Int J Pharm. 2014 Aug 25;471(1-2):516-24. doi: 10.1016/j.ijpharm.2014.05.040. Epub 2014 May 24.
The aim of this study was to explore the transdermal delivery potential of a new caffeine-containing microemulsion system. The skin permeability of caffeine (CAF) was measured in vitro using skin excised from three different animal species: rat, rabbit and pig. As shown, microemulsion containing 20% aqueous phase enhanced CAF permeation across fresh rat skin by one order of magnitude (Papp=8.2×10(-3) vs. 0.86×10(-3) cm/h; enhancement ratio=9.6). The permeability coefficient value, the cumulative permeation amount, and the percent of dose permeated after 24 h, decreased with the increase of water content from 60% to 80% in microemulsions due to the apparent increase in the droplet size. Importantly, differences were noted between caffeine transport rates across fresh and frozen/thawed pig skin whereas microemulsions delivered caffeine at similar rates across rat and rabbit skin, either fresh or frozen/thawed. It has been shown that the permeability of caffeine through frozen/thawed pig skin was abnormally high and was independent of its vehicle properties, i.e., its hydrophilic or lipophilic nature. It has been hypothesized that the reason for this abnormality is that porcine stratum corneum has a higher ceramide-to-cholesterol ratio compared to rat and rabbit skin. This unusual phenomenon observed in a non-freshly used porcine skin places a question mark on its suitability to in vitro evaluation of transdermal drug delivery systems.
本研究的目的是探索一种新型含咖啡因微乳系统的透皮给药潜力。使用从三种不同动物物种（大鼠、兔子和猪）切除的皮肤在体外测量咖啡因（CAF）的皮肤渗透性。结果表明，含20%水相的微乳使咖啡因透过新鲜大鼠皮肤的渗透增强了一个数量级（Papp = 8.2×10(-3) 对比 0.86×10(-3) cm/h；增强倍数 = 9.6）。由于微乳滴粒径明显增大，微乳中水含量从60%增加到80%时，渗透系数值、累积渗透量以及24小时后渗透剂量的百分比均下降。重要的是，观察到咖啡因在新鲜和冻融猪皮肤中的转运速率存在差异，而微乳在新鲜或冻融的大鼠和兔子皮肤中以相似的速率递送咖啡因。研究表明，咖啡因透过冻融猪皮肤的渗透性异常高，且与其载体性质（即亲水性或亲脂性）无关。据推测，这种异常现象的原因是猪角质层与大鼠和兔子皮肤相比具有更高的神经酰胺与胆固醇比例。在非新鲜使用的猪皮肤中观察到的这种异常现象对其在透皮给药系统体外评价中的适用性提出了疑问。
