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Title

Transdermal delivery of cytochrome C--A 12.4 kDa protein--across intact skin by constant-current iontophoresis

Authors
Ganem-Rondero, A
Quintanar-Guerrero, D
Published in Pharmaceutical Research. 2007, vol. 24, no. 7, p. 1360-8
Abstract PURPOSE: To demonstrate the transdermal iontophoretic delivery of a small (12.4 kDa) protein across intact skin. MATERIALS AND METHODS: The iontophoretic transport of Cytochrome c (Cyt c) across porcine ear skin in vitro was investigated and quantified by HPLC. The effect of protein concentration (0.35 and 0.7 mM), current density (0.15, 0.3 or 0.5 mA.cm(-2) applied for 8 h) and competing ions was evaluated. Co-iontophoresis of acetaminophen was employed to quantify the respective contributions of electromigration (EM) and electroosmosis (EO). RESULTS: The data confirmed the transdermal iontophoretic delivery of intact Cyt c. Electromigration was the principal transport mechanism, accounting for approximately 90% of delivery; correlation between EM flux and electrophoretic mobility was consistent with earlier results using small molecules. Modest EO inhibition was observed at 0.5 mA.cm(-2). Cumulative permeation at 0.3 and 0.5 mA.cm(-2) was significantly greater than that at 0.15 mA.cm(-2); fluxes using 0.35 and 0.7 mM Cyt c in the absence of competing ions (J ( tot ) = 182.8 +/- 56.8 and 265.2 +/- 149.1 microg.cm(-2).h(-1), respectively) were statistically equivalent. Formulation in PBS (pH 8.2) confirmed the impact of competing charge carriers; inclusion of approximately 170 mM Na(+) resulted in a 3.9-fold decrease in total flux. CONCLUSIONS: Significant amounts ( approximately 0.9 mg.cm(-2) over 8 h) of Cyt c were delivered non-invasively across intact skin by transdermal electrotransport.
Keywords Acetaminophen/administration & dosage/metabolismAdministrationCutaneousAnimalsChromatographyHigh Pressure LiquidCytochromes c/administration & dosage/chemistry/metabolismDiffusion ChambersCultureDrug Delivery Systems/methodsElectroosmosisFeasibility StudiesIontophoresisModelsMolecularMolecular WeightPermeabilityProtein ConformationSkin/metabolismSkin AbsorptionSwineTime FactorsTissue Culture Techniques
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PMID: 17457661
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CAZARES DELGADILLO, Jennyfer et al. Transdermal delivery of cytochrome C--A 12.4 kDa protein--across intact skin by constant-current iontophoresis. In: Pharmaceutical Research, 2007, vol. 24, n° 7, p. 1360-8. https://archive-ouverte.unige.ch/unige:22651

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Deposited on : 2012-08-29

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