星型硅微针阵列对化学药物的经皮促透作用

Effect of Star Silicon Microneedles on in Vitro Transdermal Drug Delivery

目的研究星型硅微针阵列对于不同油水分配系数化学药物的体外透皮传递的影响。方法采用深反应离子刻蚀技术(deep reactive ion ething,DRIE)制备硅微针阵列;选择吲哚美辛(indomethacin,IMC)、酮洛芬(ketoprofen,KTP)、美索巴莫(methocarbamol,MCM)、更昔洛韦(ganciclovir,GCV)为模型药物,对4种化学药物经微针穿刺小鼠腹部皮肤后的体外透皮特性进行比较研究。结果星型微针阵列为0.5 cm×0.5 cm,100根微针,针长200μm,成五角星型柱状结构;IMC,KTP,MCM,GCV经微针处理皮肤5 min较未处理皮肤的渗透速率分别增加4.05,4.77,6.06,12.49倍,表明硅微针对4种模型药物有明显的促透作用;实验结果显示,药物透皮传递随微针穿刺皮肤时间的延长而增强;随药物logP值降低,经微针处理皮肤的促透效果更加显著,但微针阵列经皮促透作用低于皮肤去角质处理的促透效果。结论星型硅微针阵列对水溶性药物的促透效果较脂溶性药物更加显著。将微针与其他透皮技术相结合,具有广阔的研究前景。

OBJECTIVE To study the effect of star silicon microneedle arrays on transdermal transport of chemicals with different octanol/water partition coefficient in vitro. METHODS Star silicon microneedle arrays were fabricated by the deep reactive ion ething technology. The model drugs,indomethacin, ketoprofen, methocarbamol and ganciclovir, were chosen. Cutaneous delivery in mice abdo- men skin by silicon microneedle arrays was compared. RESULTS The microneedle arrays were star shape with 100 microneedles on 10×10 array,length 200 μm. The total flux of the drugs was increased by 4. 05,4. 77,6. 06,12.49 times respectively with microneedies insertion for 5 min, compared with intact skin. Increased skin permeability appeared to occur after prolonging microneedles insertion. With the decrease of logP values of the drugs, microneedles pretreatment promoted transdermal drug delivery more effectively. However,the drug permeability through skin with microneedle pretreatment was less than that though skin with stratum corneum ablated. CONCLUSION Star silicon microneedle arrays can be used to deliver chemicals through the skin, and the permeability of the water soluble drugs was enhanced more significantly than that of the liposoluble ones. This study suggested that microneedles could be an effective means for deliverying chemicals and maximise drug flux combining with other transdermal techniques.