电穿孔技术促进甲硝唑家兔在体经皮吸收的研究

Effects of electroporation on transdermal delivery of metronidazole

目的研究电穿孔技术对甲硝唑家兔在体经皮吸收的影响。方法以甲硝唑为模型药物,通过采用HPLC法测定不同时间的血药浓度,研究电穿孔技术(指数衰减脉冲,电容器电容为22μF,脉冲电压为380 V,脉冲率为4个.m in-1,脉冲时间为1.74 ms,脉冲数为50)对小分子,非解离型药物在家兔腹部皮肤在体经皮吸收的影响。结果与被动扩散相比,电穿孔可使甲硝唑迅速透过皮肤吸收进入血液,0.5 h时就可使血药浓度达到(8.56±3.63)nmol.mL-1,被动扩散则需2 h时才可在血中测到药物,浓度为(4.35±0.20)nmol.mL-1。2 h以后,被动扩散与电穿孔的透皮吸收差异无显著性。结论电穿孔可迅速促进小分子非解离型药物甲硝唑的经皮吸收,缩短药物经皮吸收的时滞。

Objective To study the enhancement effect of electroporation on the in vivo transdermal delivery of metronidazole. Methods Metronidazole was used as a model drug and the effect of eleetroporation （ exponential voltage pulses 380 V with 1.74 ms pulse time, pulse frequency 4 pulses·min^-1） was investigated on rabbit abdominal skin. The serum concentrations of metronidazole were determined. Results The transdermal delivery of metronidazole was rapidly increased by eleetroporation, and serum drug concentration during eleetroporation reached （8.56±3.63） nmol·mL^-1 at 0.5 h, （4.35±0.20） nmol·mL^-1 at 2 h. However, during passive diffusion, the serum drug concentration was under the detection limit during the first 2 h, and there were no obvious differences between eleetroporation and passive diffusion after 2h. Conclusion The transdermal delivery of metronidazole is rapidly enhanced by electroporation.