Oleic Acid As Optimizer of the Skin Delivery of 5-aminolevulinic Acid in Photodynamic Therapy

Purpose: In photodynamic therapy (PDT), topically applied aminolevulinic acid (5-ALA) is converted to protoporphyrin IX (PpIX), which upon light excitation induces tumor destruction. To optimize 5-ALA-PDT via improving the highly hydrophilic 5-ALA limited penetration into the skin, we propose the use of the known skin penetration enhancer, oleic acid (OA).

Methods: In vitro skin penetration and retention of 5-ALA (1% w/w) were measured in the presence or absence of OA (2.5, 5.0, and 10.0% w/w) in propylene glycol (PG) using porcine ear skin as the membrane. In vivo accumulation of PpIX, 4 h after application, was determined fluorometrically in healthy mice skin by chemical extraction of skin samples. In vivo PpIX fluorescence kinetics was also investigated by noninvasive techniques using an optical fiber probe, for 30 min up to 24 h after topical application of 1.0% 5-ALA + 10.0% OA in PG on hairless mice skins.

Results: The flux and in vitro retention of 5-ALA in viable epidermis increased in the presence of 10.0% (w/w) OA. The amounts of PpIX, evaluated both by chemical tissue extractions and in vivo measurements by an optical fiber probe, increased after applying 5-ALA formulations containing 5.0 or 10.0% OA. Moreover, in vivo kinetic studies showed an increase in skin PpIX accumulation when formulations containing 10% OA were used; PpIX accumulation was also maintained longer compared to controls.

Conclusions: Both in vitro and in vivo results show the OA potential as an optimizer of 5-ALA skin delivery.