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.