title: Transdermal delivery of cytochrome C--A 12.4 kDa protein--across intact skin by constant-current iontophoresis.
abstract: OBJECTIVE
  To demonstrate the transdermal iontophoretic delivery of a small (12.4 kDa) protein across intact skin.
  
  
  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.
authors: School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, 30 Quai Ernest Ansermet, 1211, Geneva, Switzerland.
authors: J
authors: J
authors: Cázares-Delgadillo
authors: A
authors: A
authors: Naik
authors: A
authors: A
authors: Ganem-Rondero
authors: D
authors: D
authors: Quintanar-Guerrero
authors: Y N
authors: YN
authors: Kalia
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000378:metabolism; D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D045304:Cytochromes c / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems / Q000379:methods*; D053841:Electroosmosis; D005240:Feasibility Studies; D007478:Iontophoresis; D008958:Models, Molecular; D008970:Molecular Weight; D010539:Permeability; D011487:Protein Conformation; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D000082:Acetaminophen; D045304:Cytochromes c