Transdermal iontophoresis of small molecules with cotransport of polystyrene sulfonate oligomers

The fluxes of ionic and nonionic probe permeants across hairless mouse skin (HMS) were induced by direct current (DC) iontophoresis and used to characterize the transport pathways of the epidermal membrane under two conditions: 1) with phosphate buffered saline (PBS) in both the anodal and cathodal chamber, referred to as baseline studies; and 2) with PBS in the anodal chamber and with sodium polystyrene sulfonate (PSS) in the cathodal chamber. Probe permeants used in these experiments were nonionic permeants (urea, mannitol, and raffinose), monovalent cationic permeants (sodium, tetraethylammonium, and tetraphenylphosphonium ions), and monovalent anionic permeants (chloride, salicylate, and taurocholate ions). The permeability coefficients of the nonionic probe permeants increased up to sixfold with sodium PSS in the cathodal chamber. Increases in the permeability coefficients of nonionic permeants were independent of the sodium PSS concentrations (sodium PSS concentrations investigated included 1.37, 13.7 and 137 mg/mL). Permeability coefficients of the cationic probe permeants also increased up to threefold relative to baseline results and remained constant, independent of the sodium PSS concentration in the cathodal chamber. The permeability coefficients of the anionic probe permeants increased slightly relative to baseline results with 1.37 mg/mL sodium PSS in the cathodal chamber and then decreased as the concentration of sodium PSS in the cathodal chamber increased. In addition to investigating the transport behavior of the probe permeants, the modified iv Nernst-Planck model was used as a theoretical framework for interpreting the data and calculating the effective pore radius (Rp) of pathways available to the probe permeants during iontophoresis. Under baseline conditions the Rp values obtained using nonionic permeant transport data ranged from 7 - 13 Å; with sodium PSS in the cathodal chamber Rp values ranged from 9 - 27 Å. The results of theoretical Nernst-Planck calculations also helped to explain the transport behavior of the cationic probe permeants and confirmed, based on cationic probe permeant data, that with sodium PSS in the cathodal chamber Rp values were in the same range (20 - 30 Å) as those calculated in baseline studies.