Cutaneous iontophoresis of μ-conotoxin CnIIIC—A potent Na_V1.4 antagonist with analgesic, anaesthetic and myorelaxant properties

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• 作者：Sergio del Rí ; o-Sancho^a ; Cecile Cros^b ; Bethsabé ; e Coutaz^b ; Muriel Cuendet^a ; Yogeshvar N. Kalia^a ; ^{yogi.kalia@unige.ch}
• 关键词：Biodistribution ; Conopeptide ; Cutaneous ; Iontophoresis ; Topical delivery ; XEP-018
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：25 February 2017
• 年：2017
• 卷：518
• 期：1-2
• 页码：59-65
• 全文大小：1086 K
• 卷排序：518

文摘

Cutaneous iontophoretic delivery of μ-conotoxin CnIIIC (XEP), a potent peptide antagonist of the NaV1.4 sodium channel, was investigated using porcine ear skin and validated using human abdominal skin. Initial results demonstrated that cutaneous deposition of XEP following iontophoresis was superior to passive delivery and increased with current density. XEP deposition after iontophoresis at 0.1, 0.3 and 0.5 mA/cm2 for 2 h and 4 h was 22.4 ± 0.4, 34.5 ± 1.4, 57.4 ± 7.6 μg/cm2 and 30.6 ± 5.4, 53.9 ± 17.2, 90.9 ± 30.8 μg/cm2, respectively (cf. corresponding passive controls – 9.8 ± 1.1 and 16.9 ± 1.0 μg/cm2). Moreover, tape-stripping studies showed that XEP was mainly adsorbed on the skin surface when administered passively. Co-iontophoresis of acetaminophen demonstrated that XEP was present in the skin as it significantly reduced convective solvent flow as evidenced by the ∼7-fold decrease in acetaminophen permeation. Shorter duration iontophoresis (15, 30 and 60 min) was performed and the effect of current density (0.1, 0.3 and 0.5 mA/cm2) and concentration (0.1 and 1 mM) investigated. Skin deposition of XEP was already quantifiable after iontophoresis for 15 min at the lower concentration. There was no statistically significant difference between XEP deposition in porcine and human skin. Confocal laser scanning microscopy enabled post-iontophoretic visualization of FITC-labelled XEP in the epidermis.