Xu Ting, Xu Yue-Hong, Wei Min-Yan, Deng Li-He, Wu Chuan-Bin
School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
Yao Xue Xue Bao. 2011 Jun;46(6):713-9.
In vitro percutaneous delivery of hepatitis B vaccines was investigated in order to assess the penetration of vaccine under passive diffusion and iontophoresis conditions. The study was carried out using Franz vertical diffusion cell through the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the cumulative amount of permeation and the retention amount of drug in skin. Passive diffusion alone resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1 +/- 0.1) ng x cm(-2) and (2.3 +/- 0.1) ng x cm(-2) after 24 h when the initial concentration of vaccine in the donor compartment was 23 microg x mL(-1) and 46 microg x mL(-1), respectively. After removing the stratum corneum, the permeation and retention amount of hepatitis B vaccines increased to (383.7 +/- 86.2) ng x cm(-2) and (16.8 +/- 4.6) ng x cm(-2), respectively, 171.6-folds and 2.1-folds more than that from its intact skin with the drug loaded at 46 microg x mL(-1). Iontophoresis induced a significant increase of cumulative and retention amount of hepatitis B vaccines through the skin (P < 0.05). Application of iontophoresis significantly enhanced the permeation of hepatitis B vaccines (P < 0.05) by 2.7-folds and 6.6-folds for the intact skin, and by 1.6-folds and 1.8-folds for the tape-stripped skin with initial drug loading of 23 microg x mL(-1) and 46 microg x mL(-1), respectively. Iontophoresis also significantly increased the amount of drug retained in the skin. After applying iontophoresis for 6 h, the amount of skin retention was nearly the same as passive diffusion for 24 h both from intact skin [(16.8 +/- 4.6) ng x cm(-2) vs (13.3 +/- 5.4) ng x cm(-2)] (P > 0.05) and tape-stripped skin [(36.7 +/- 14.1) ng x cm(-2) vs (26.8 +/- 11.2) ng x cm(-2)] (P > 0.05). Overall, these findings revealed that the transportation efficiency of bioactive substance like hepatitis B vaccines may be improved by iontophoresis, which can be potentially used in the field of transcutaneous immunization.
为评估乙肝疫苗在被动扩散和离子导入条件下的渗透情况，对其体外经皮给药进行了研究。该研究使用Franz垂直扩散池，透过斯普拉格-道利（SD）大鼠的腹部无毛皮肤进行。采用酶联免疫吸附测定（ELISA）法测定药物在皮肤中的累积渗透量和滞留量。单独的被动扩散导致乙肝疫苗的皮肤渗透和滞留较少，当供体室中疫苗的初始浓度分别为23μg/mL和46μg/mL时，24小时后仅为（2.1±0.1）ng/cm²和（2.3±0.1）ng/cm²。去除角质层后，乙肝疫苗的渗透量和滞留量分别增加到（383.7±86.2）ng/cm²和（16.8±4.6）ng/cm²，分别比初始药物浓度为46μg/mL时完整皮肤的相应值高171.6倍和2.1倍。离子导入显著增加了乙肝疫苗通过皮肤的累积量和滞留量（P<0.05）。对于初始药物浓度为23μg/mL和46μg/mL的完整皮肤，离子导入分别使乙肝疫苗的渗透量显著提高（P<0.05）2.7倍和6.6倍；对于胶带去除皮肤，分别提高1.6倍和1.8倍。离子导入还显著增加了皮肤中保留的药物量。离子导入6小时后，完整皮肤[（16.8±4.6）ng/cm²对（13.3±5.4）ng/cm²]（P>0.05）和胶带去除皮肤[（36.7±14.1）ng/cm²对（26.8±11.2）ng/cm²]（P>0.05）的皮肤滞留量与被动扩散24小时的几乎相同。总体而言，这些发现表明，离子导入可提高乙肝疫苗等生物活性物质的转运效率，这在经皮免疫领域具有潜在应用价值。
