Background: Cetuximab (CTX) is a glycosylated anti-EGFR monoclonal antibody of great interest in the treatment of non-melanoma skin cancers. Its intravenous administration is associated with severe side effects. This is the first report on the noninvasive iontophoretic-targeted topical delivery of CTX to skin.Methods: Iontophoretic transport of CTX (0.5 mA/cm2) was studied as a function of formulation pH (4, 5.5 and 7) and duration of current application (2, 4 and 8 h). CTX cutaneous biodistribution was determined; electrotransport mechanisms and penetration pathways were investigated.Results: Electrophoretic mobility measurements of CTX isoforms and co-iontophoresis of acetaminophen at each pH demonstrated that CTX electrotransport was due to electroosmosis: despite an ~8-fold reduction in charge, CTX skin deposition was greater at pH 7 than pH 4 (8.974 ± 1.952 and 0.482 ± 0.165 μg/mm3) - consistent with the increased electroosmotic flow at pH 7. Iontophoresis of an Alex488-CTX conjugate showed that skin penetration occurred by the intercellular and follicular routes. Therapeutic concentrations of CTX in the viable epidermis, upper dermis and lower dermis were achieved following iontophoresis for 2, 4 and 8 h, respectively.Conclusion: The results demonstrate the topical delivery of a 152 kDa monoclonal antibody into skin in a targeted, controlled and entirely noninvasive manner.

中文翻译：

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西妥昔单抗向皮肤的非侵入性靶向离子电渗疗法。

背景：西妥昔单抗（CTX）是一种糖基化的抗EGFR单克隆抗体，在治疗非黑素瘤皮肤癌中非常受关注。其静脉内给药与严重的副作用有关。这是关于CTX以非侵入性靶向靶向局部递送至皮肤的第一篇报道。方法：研究了CTX的离子电渗转运（0.5 mA / cm2）与制剂pH（4、5.5和7）和当前应用时间的关系（2、4和8小时）。确定了CTX的皮肤生物分布；结果：CTX异构体的电泳迁移率测量和对乙酰氨基酚在每个pH值的共离子电泳表明CTX电迁移归因于电渗：尽管电荷减少了约8倍，pH 7时CTX的皮肤沉积大于pH 4（8.974±1.952和0.482±0.165μg/ mm3）-与pH 7时电渗流量的增加一致。Alex488-CTX偶联物的电渗表明，皮肤渗透是由细胞间和卵泡途径。离子电渗疗法分别在2、4和8小时后达到了活表皮，上层真皮和下层真皮中CTX的治疗浓度。结论：结果表明，靶向性，可控性和靶向性可将152 kDa单克隆抗体局部递送至皮肤。完全无创的方式。