title: Effects of ethanol and diclofenac on the organization of hydrogenated phosphatidylcholine bilayer vesicles and their ability as skin carriers.
abstract: In this study, the effects of ethanol and/or diclofenac on vesicle bilayer structure have been studied. Liposomes with hydrogenated soy phosphatidylcholine, cholesterol and two different concentrations of diclofenac sodium (5 and 10 mg/ml) were obtained. In addition, ethanol was mixed in the water phase at different concentrations (5, 10 and 20 % v/v) to obtain ethosomes. To characterize vesicles, rehological analysis were carried out to investigate the intervesicle interactions, while bilayer structure was evaluated by small- and wide-angle X-ray scattering. Finally, the ethanol and/or diclofenac concentration-dependent ability to improve diclofenac skin delivery was evaluated in vitro. The addition of 20 % ethanol and/or diclofenac led to solid-like ethosome dispersion due to the formation of a new intervesicle structure, as previously found in transcutol containing vesicle dispersions. However, when using 5-10 % of ethanol the induction to form vesicle interconnections was less evident but the simultaneous presence of the drug at the highest concentration facilitated this phenomenon. Ethosomes containing the highest amount of both, drug (10 mg/ml) and ethanol (20 % v/v), improved the drug deposition in the skin strata and in the receptor fluid up to 1.5-fold, relative to liposomes. Moreover this solid-like formulation can easily overcome drawbacks of traditional liquid liposome formulations which undergo a substantial loss at the application site.
authors.affiliation: Department Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Castangia
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.forename: Pietro
authors.initials: P
authors.lastname: Matricardi
authors.forename: Ana
authors.initials: A
authors.lastname: Catalán-Latorre
authors.forename: Amparo
authors.initials: A
authors.lastname: Nácher
authors.forename: Octavio
authors.initials: O
authors.lastname: Diez-Sales
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernàndez-Busquets
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
mesh_terms: D000818:Animals; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006859:Hydrogen / Q000737:chemistry*; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D012867:Skin / Q000378:metabolism*; D013552:Swine
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D004008:Diclofenac; D000431:Ethanol; D006859:Hydrogen