Abstract

The goals of this study were to quantitatively evaluate the iontophoretic delivery of a homologous series of cationic aminolevulinic acid (ALA) esters and to determine the contributions of electromigration and electroosmosis to their overall electrotransport in vitro. Anodal iontophoretic transport of ALA esters through porcine skin in vitro was followed for 2 h at a constant current of 0.5 mA/cm2. To deduce the mechanism, the concomitant transport of an electroosmotic marker, mannitol, was also assessed. Positively charged ALA esters of moderate lipophilicity showed increased iontophoretic flux through the skin. A more than 50‐fold enhancement as compared with the zwitterionic parent ALA was observed for the methyl ester. As the size and lipophilicity of the ester increased, the efficiency of electrotransport decreased. The most lipophilic esters reduced the electroosmotic flow presumably because of the association of these cations with negative charges in the skin. Iontophoresis of methyl‐ALA and hexyl‐ALA also increased the amount of prodrug delivered into the skin. In summary, significant topical delivery of ALA esters can be achieved by iontophoresis, and transport into and across the skin was greatly enhanced compared with that of ALA itself. It remains to be seen whether this enhanced local bioavailability of the protoporphyrin prodrug can allow improved photodynamic therapy for the treatment of skin cancer.

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