Cutaneous iontophoresis of μ-conotoxin CnIIIC—A potent Na V 1.4 antagonist with analgesic, anaesthetic and myorelaxant properties
| Autor: | Yogeshvar N. Kalia, Cecile Cros, Bethsabée Coutaz, Sergio del Río-Sancho, Muriel Cuendet |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Biodistribution Swine Skin Absorption Analgesic Pharmaceutical Science Conotoxins/administration & dosage/pharmacokinetics Human skin Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Skin/metabolism NAV1.4 Voltage-Gated Sodium Channel ddc:615 Neuromuscular Agents/administration & dosage/pharmacokinetics Iontophoresis Chemistry Sodium channel Voltage-Gated Sodium Channel Blockers/administration & dosage/pharmacokinetics Antagonist Reproducibility of Results Permeation Acetaminophen Cutaneous 030104 developmental biology Anesthesia Administration Analgesics/administration & dosage/pharmacokinetics Anesthetics/administration & dosage/pharmacokinetics medicine.drug |
| Zdroj: | International Journal of Pharmaceutics, Vol. 518, No 1-2 (2017) pp. 59-65 |
| ISSN: | 0378-5173 |
| Popis: | 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 0.5mA/cm(2) for 2h and 4h was 22.4±0.4, 34.5±1.4, 57.4±7.6μg/cm(2) and 30.6±5.4, 53.9±17.2, 90.9±30.8μg/cm(2), respectively (cf. corresponding passive controls - 9.8±1.1 and 16.9±1.0μg/cm(2)). 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 60min) was performed and the effect of current density (0.1, 0.3 and 0.5mA/cm(2)) and concentration (0.1 and 1mM) investigated. Skin deposition of XEP was already quantifiable after iontophoresis for 15min 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. |
| Databáze: | OpenAIRE |
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