Marconi B, Mancini F, Colombo P, Allegra F, Giordano F, Gazzaniga A, Orecchia G, Santi P
Dipartimento Farmaceutico, Viale delle Scienze, University of Parma, 43100, Parma, Italy.
J Control Release. 1999 Aug 5;60(2-3):261-8. doi: 10.1016/s0168-3659(99)00080-2.
The aim of this work was to study in vitro khellin distribution into human skin after passive or iontophoretic transport. The experiments were performed on excised human skin, using vertical Franz-type diffusion cells. The effects of current application and reservoir pH were studied. At the end of the experiments the skin was sliced thinly and the drug was extracted and analyzed by HPLC. The results showed that khellin is able to penetrate through stratum corneum, to reach basal epidermis and upper dermis. The application time proved to be an important parameter. Current application (30 min; 0.5 mA/cm(2)), with a donor at pH 7.0, favored khellin accumulation even if the drug is not ionized. On the contrary, the use of a formulation at pH 3.2 inhibited drug accumulation. Leaving the drug reservoir in contact with the skin for 30 min after current application led to a dramatic increase of khellin concentration. A combination of dermal iontophoresis and passive diffusion is then a useful technique to govern khellin distribution in the skin.
本研究旨在探讨凯林在被动或离子导入转运后在人皮肤中的体外分布情况。实验采用垂直式Franz型扩散池，在离体人皮肤上进行。研究了电流施加和储库pH值的影响。实验结束后，将皮肤切成薄片，提取药物并用高效液相色谱法进行分析。结果表明，凯林能够穿透角质层，到达基底表皮和真皮上层。给药时间被证明是一个重要参数。在供体pH值为7.0的情况下施加电流（30分钟；0.5 mA/cm²），即使药物未电离，也有利于凯林的蓄积。相反，使用pH值为3.2的制剂会抑制药物蓄积。在施加电流后让药物储库与皮肤接触30分钟会导致凯林浓度显著增加。因此，皮肤离子导入和被动扩散相结合是控制凯林在皮肤中分布的一种有用技术。
