Oleic acid as optimizer of the skin delivery of 5-aminolevulinic acid in photodynamic therapy.
OBJECTIVE
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.
Pierre
Maria Bernadete Riemma
MB
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, São Paulo, San Paul, Brazil.
Ricci
Eduardo
E
Tedesco
Antonio Cláudio
AC
Bentley
Maria Vitória Lopes Badra
MV
D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000627:therapeutic use*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005456:Fluorescent Dyes; D005470:Fluorometry; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D019301:Oleic Acid / Q000494:pharmacology*; D010047:Ovalbumin / Q000378:metabolism; D010592:Pharmaceutic Aids / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
D005456:Fluorescent Dyes; D010592:Pharmaceutic Aids; D017319:Photosensitizing Agents; D015842:Serine Proteinase Inhibitors; D019301:Oleic Acid; D000622:Aminolevulinic Acid; D010047:Ovalbumin