title: Ethosomes for enhanced skin delivery of griseofulvin.
abstract: Griseofulvin (GRF) is an important antifungal drug with low bioavailability and, for this reason, a topical formulation with a targeted action and minimal systemic effects, appears to be a preferable solution. GRF poor solubility has limited the development of topical formulations and their release to the market. The aim of this work was to prepare a new GRF formulation for topical application using lipid-based nanosystems; to study its permeation and penetration, cell viability and to evaluate its therapeutic action. Ethosomal systems composed of soy bean phosphatidylcholine, ethanol and water were prepared for incorporating GRF. After the characterization of the vesicles in terms of size, charge and penetrability, permeation through newborn pig using Franz diffusion cells was conducted. Cell viability at different concentrations of the chosen formulation was determined. At last, skin adapted agar diffusion test was performed to assess the therapeutic efficacy of the formulation. GRF vesicles had mean size of 130nm. Permeation and penetration assays revealed that GRF-loaded ethosomes have an adequate profile to be used in a topical formulation since drug retention in the stratum corneum was achieved. Cell viability tests proved this formulation presented no cytotoxicity to HaCaT cells for concentrations below 50μg/mL. The skin diffusion test evidenced the potential of developed formulation to target skin dermatophytes. The results obtained in this study contribute to a new perspective in topical treatment of fungal infections.
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: jmmarto@ff.ulisboa.pt.
authors.forename: Joana
authors.initials: J
authors.lastname: Marto
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: catarina.vitor@campus.ul.pt.
authors.forename: Catarina
authors.initials: C
authors.lastname: Vitor
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: analuisacoelhoguerreiro@yahoo.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Guerreiro
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: cristianaseverino@hotmail.com.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Severino
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: carlavania@ff.ul.pt.
authors.forename: Carla
authors.initials: C
authors.lastname: Eleutério
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: andreiaascenso@ff.ulisboa.pt.
authors.forename: Andreia
authors.initials: A
authors.lastname: Ascenso
authors.affiliation: Universidade de Lisboa, Faculdade de Farmácia, Nano2B Group of Research Institute for Medicines (iMed.ULisboa), Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: ssimoes@ff.ulisboa.pt.
authors.forename: Sandra
authors.initials: S
authors.lastname: Simões
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006118:Griseofulvin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009181:Mycoses / Q000188:drug therapy; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
chemical_list: D000935:Antifungal Agents; D006118:Griseofulvin
keywords: Ethosomes; Griseofulvin; Skin delivery; Skin superficial fungal infections; Skin targeting