Testosterone ethosomes for enhanced transdermal delivery
Testosterone ethosomes for enhanced transdermal delivery
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DOI：
10.1080/10717540500176910
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发表时间：
2005-09-01
期刊：
影响因子：
6
通讯作者：
Touitou, E
中科院分区：
文献类型：
--
作者：
Ainbinder, D;Touitou, E
随着年龄的增长，男性睾酮水平的生理性下降会引起各种具有临床意义的变化。目前的睾酮替代疗法主要基于经皮非贴片给药系统。这些产品的缺点是无法在非常大的区域内应用，以达到所需的激素水平。本研究的目的是设计和测试一种使用乙醇小体的睾酮非贴片制剂，以促进经皮吸收。用透射电子显微镜和动态光散射表征了乙醇体剂的结构和尺寸分布，并用超速离心法测定了包封率。为了评估这种给药系统增强睾酮在皮肤中渗透的可行性，首先对大鼠的全身吸收与目前使用的凝胶(androGel(R))进行了比较。此外，还对男性使用酒精后的睾酮血药浓度进行了理论上的估计。为此，我们进行了人体皮肤的体外渗透实验，以确定睾酮的皮肤渗透值。在这些实验的设计中，测量了睾酮在不同溶液中的溶解度，并用共聚焦激光扫描显微镜评估了接收介质对皮肤屏障功能的影响。理论估算表明，在40 cm(2)的面积上应用醇胺制剂可使人体血浆睾酮浓度达到生理范围的上半部分。这一面积比目前的非贴片制剂所需的面积小约10倍。我们的工作表明，乙醇制剂可以增强睾酮的全身吸收，并可用于设计新的产品，以解决目前睾酮替代疗法的缺点。
Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel(R)). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm(2). This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.