【摘要】 在电致孔下的经皮传输是胰岛素给药的重要途径。表面活性剂十六烷基三甲基溴化铵(CTAB)可阻止胰岛素聚集,减小经皮渗透阻力;但CTAB和电致孔采用的高压脉冲将影响胰岛素的活性,因而研究了在峰值电压为200~400V、长度为1~12ms的脉冲下,CTAB和电脉冲对胰岛素稳定性的影响。结果表明,随溶液中CTAB含量的升高,胰岛素的聚集程度降低,但失活比例迅速增加;当CTAB与胰岛素的物质量比达到60:1时,即使在小强度脉冲下,失活胰岛素的比例也接近80%。胰岛素的变性主要发生在电极周围,与电极表面积有关。采用透析膜将电极与胰岛素分子隔离的方法可克服胰岛素在脉冲下的失活。此时,脉冲后活性胰岛素比例可达80%,且该值随CTAB含量的增加仅有轻微下降;而以活性胰岛素计量的电致孔下的经皮渗透速率则提高2~3倍。更多还原

【Abstract】 Electroporation is a potential approach for the transdermal delivery of insulin. Surfactant CTAB can be used to inhibit the self-association of insulin, which results in the decrease of the mass transfer resistance. However, both the high-voltage pulses of the electroporation and the presence of CTAB might induce the denaturalization of insulin. In present study, the effects of CTAB and electrical pulses on the bioactivity of insulin were investigated by using the pulses with the voltage of 200~400 V and the duration of 1~12 ms. The results show that with the rise of CTAB concentration the aggregation level of insulin becomes lower while its denaturalization accelerates rapidly. About 80% insulin is denatured when the CTAB-to-insulin molar ratio reaches 60:1 even as the intensity of the pulse is very small. The denaturalization of insulin mainly occurs near the electrodes and depends on the surface area of the electrodes. Thus, the denaturalization of insulin during electroporation can be alleviated by isolating the electrodes from the insulin molecules with dialysis membrane. In this way, over 80% of insulin remains active after electroporation and the rise of CTAB concentration results in little increase of the denatured insulin, while the transdermal flux rate counted by active insulin is improved by 2~3 fold.更多还原