MECHANISM AND ENHANCEMENT OF TRANSDERMAL ABSORPTION

这项研究的长期目标是了解运输 透皮吸收机制，使得更可靠和 可以设计可预测的药物输送系统。 因为 持续需要安全有效的药物来调节生育力， 调查的重点是避孕药具的发放。 毒品 该项目的具体目标是：（1）评估 药物结构与化学性质之间的关系， 人体经皮吸收;（2）确定速率- 作为药物功能的皮肤渗透的限制过程 结构和属性;（3）定义 体内透皮吸收可以通过使用渗透 （4）了解皮肤的机制， 渗透“增强剂”功能。 实验是在 在人体内和体外使用在整形期间切除的人皮肤 手术 在存在和不存在以下情况下的渗透测量： “增强剂”利用新的质量平衡和表面消失 局部应用放射性标记药物后的技术。 在闭塞下的局部“增强剂”效应通过以下方式监测： 经表皮水分损失和激光多普勒测速仪。 药物 穿过皮肤和在皮肤内的定位是通过 反射傅里叶变换红外光谱（FTIR）。 地位 和角质层脂质的扰动（通过“增强剂”） 通过FTIR和差示扫描来评估结构 量热法 在分子水平上探讨 角质层脂质组成和组织，气液 建立、操作角质形成细胞培养物， 通过物理技术检查。 模型实验使用封闭的 由角质层脂质制备的囊泡同时 加强对文化的研究。 总的来说， 因此，该项目旨在建立透皮机制， 通过明智地应用生物物理学， 生物工程和生物化学技术的解释， 药物在人体皮肤中的渗透及其增强作用。

The long term goal of this research is to understand the transport mechanisms of transdermal absorption such that more reliable and predictable drug delivery systems may be designed. Because of a continued need for safe and effective agents to regulate fertility, the investigation is focussed on the delivery of contraceptive drugs. The specific aims of the project are: (1) to evaluate the relationship between drug structure and chemical properties and percutaneous absorption in humans; (2) to determine the rate- limiting process in skin penetration as a function of drug structure and properties; (3) to define the level by which transdermal absorption in vivo may be increased using penetration `enhancers'; (4) to comprehend the mechanism(s) by which skin penetration `enhancers' function. Experiments are performed in vivo in man and in vitro using human skin excised during plastic surgery. Penetration measurements in the presence and absence of `enhancers' utilize novel mass balance and surface disappearance techniques following topical application of radiolabeled drug. Local `enhancer' effects under occlusion are monitored by transepidermal water loss and laser Doppler velocimetry. Drug passage across and localization within the skin is measured by reflectance Fourier-transform infrared spectroscopy (FTIR). Status and perturbations (by the `enhancers') to stratum corneum lipid structure are assessed by FTIR and differential scanning calorimetry. To probe, at a molecular level, the significance of stratum corneum lipid composition and organization, an air-liquid keratinocyte culture is established, manipulated and subjected to examination by physical techniques. Model experiments using closed vesicles prepared from stratum corneum lipids are concurrently undertaken to reinforce the studies in culture. Overall, therefore, the project aims to establish mechanisms of transdermal absorption by the judicious application of biophysical, bioengineering and biochemical techniques to the interpretation of drug penetration and its enhancement through human skin in vivo.