title: In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.
abstract: 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
authors.affiliation: 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
authors.forename: Fernanda Scarmato
authors.initials: FS
authors.lastname: De Rosa
authors.forename: Antônio Cláudio
authors.initials: AC
authors.lastname: Tedesco
authors.forename: Renata Fonseca Vianna
authors.initials: RF
authors.lastname: Lopez
authors.forename: Maria Bernadete Riemma
authors.initials: MB
authors.lastname: Pierre
authors.forename: Norbert
authors.initials: N
authors.lastname: Lange
authors.forename: Juliana Maldonado
authors.initials: JM
authors.lastname: Marchetti
authors.forename: Jeane Cristina Gomes
authors.initials: JC
authors.lastname: Rotta
authors.forename: Maria Vitória Lopes Badra
authors.initials: MV
authors.lastname: Bentley
mesh_terms: 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
chemical_list: D004952:Esters; D000622:Aminolevulinic Acid