離子電透入法與電破法於體外與體內對 Indomethacin 之經皮吸收的影響   全文下載

The Effects of Iontophoresis and Electroporation on Transdermal Delivery of Indomethacin Evaluated In Vitro and In Vivo

本研究目的在於評估離體與活體之情況下， 離子電透入法（iontophoresis）與電破法（electroporation）促進indomethacin穿透數種障壁之經皮吸收的效果。離體實驗下，以纖維半透膜、大白鼠皮、豬皮與人類表皮為穿透障壁；而活體實驗中，則以大白鼠為動物模式，並以其血中濃度為評估依據。在離體實驗中，相較於對照的被動擴散之結果，離子電透入法於使用中與使用後皆可有效促進indomethacin穿透實驗中所使用的障壁。在某些情況下，電破法可增加第12小時的藥物累積穿透量。相對於單獨使用離子電透入法或是電破法，兩者合併促進可產生加成之效果。就第12小時累積穿透量、0至3小時流通量與穩定期（steady-state）之流通量而言，離子電透入法與合併法可減少不同物種間經皮吸收之穿透量的差異性。活體實驗結果之趨勢與離體實驗結果相似。離子電透入法與合併法皆可增加indomethacin的血中濃度對於時間之曲線下面積。實驗結果更發現使用電破法合併離子電透入法會導致表皮水份散失量顯著且暫時性的增加。總之，離體實驗結果之趨勢確實與活體實驗之結果呈現相關性。

The objective of this study was to evaluate the transdermal delivery of indomethacin in vitro and in vivo enhanced by iontophoresis and/or electroporation through several barriers. Excised Wistar rat skin, pig skin, human epidermal membrane and cellulose membrane were tested for the in vitro indomethacin permeation, whereas drug concentration of in the plasma was analyzed to monitor the percutaneous absorption in Wistar rat in vivo. Iontophoresis enhanced the in vitro transdermal delivery of indomethacin as compared to the passive diffusion. Pulsing of high voltages, as known as electroporation, followed by iontophoresis did result in a synergistic effect in contrast to iontophoresis or electroporation alone. The in vitro result indicated that higher drug permeation could be induced during and after the application of iontophoresis. In some case, the permeation could benefit from the electroporation in term of cumulative amount within 12 hr. Furthermore, the combination of electroporation and iontophoresis resulted in a higher permeation amount than iontophoresis or electroporation alone did. Both iontophoresis and the combination protocol could reduce interspecies difference in vitro. The in vivo results were similar to that of in vitro ones. Iontophoresis and electroporation/iontophoresis resulted in higher AUC (area under curve) of blood concentration profiles of indomethacin. In addition, the combination protocol significantly induced higher transepidermal water loss (TEWL). It is concluded that the in vivo permeation results did correspond to the enhancement efficiency of the in vitro experiments.