title: Development of microemulsions to topically deliver 5-aminolevulinic acid in photodynamic therapy.
abstract: The aim of this study was to obtain and to characterize microemulsions containing 5-aminolevulinic acid (5-ALA) and to investigate the influence of these systems in drug skin permeation for further topical photodynamic therapy (PDT). 5-ALA was incorporated in water-in-oil (W/O), bicontinuous (Bc), and oil-in-water (O/W) microemulsions obtained by the titration of ethyl oleate and PEG-8 caprylic/capric glycerides:polyglyceryl-6 dioleate (3:1) mixtures with water. Selected systems were characterized by conductivity, viscosity, size of the droplets, and drug release. The stability of the drug in the microemulsions was also assessed. Moreover, the in vitro and in vivo skin permeation of 5-ALA was investigated using diffusion cells and confocal scanning laser microscopy (CSLM), respectively. Despite the fact that the O/W microemulsion decreased the 5-ALA diffusion coefficient and retarded the drug release, it also significantly increased the in vitro drug skin permeation when compared to other 5-ALA carriers. It was observed by CSLM that the red fluorescence of the skin increased homogeneously in the deeper skin layers when the 5-ALA microemulsion was applied in vivo, probably due to the formation of the photoactive protoporphyrin IX. The microemulsion developed carried 5-ALA to the deeper skin layers, increasing the red fluorescence of the skin and indicating the potentiality of the system for topical 5-ALA-PDT.
authors.affiliation: Department of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Luciana Mattoso Pires de Campos
authors.initials: LM
authors.lastname: Araújo
authors.forename: José Antônio
authors.initials: JA
authors.lastname: Thomazine
authors.forename: Renata Fonseca Vianna
authors.initials: RF
authors.lastname: Lopez
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D004655:Emulsions; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D010778:Photochemotherapy / Q000379:methods / Q000639:trends*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology; D013552:Swine
chemical_list: D004655:Emulsions; D000622:Aminolevulinic Acid