In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.
In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT
De Rosa
Fernanda Scarmato
FS
Departamento de Ciências Farmacêuticas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil
Tedesco
Antônio Cláudio
AC
Lopez
Renata Fonseca Vianna
RF
Pierre
Maria Bernadete Riemma
MB
Lange
Norbert
N
Marchetti
Juliana Maldonado
JM
Rotta
Jeane Cristina Gomes
JC
Bentley
Maria Vitória Lopes Badra
MV
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D004952:Esters; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010778:Photochemotherapy / Q000379:methods*; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology
D004952:Esters; D000622:Aminolevulinic Acid