title: Close-packed vesicles for diclofenac skin delivery and fibroblast targeting.
abstract: Concentrated and interconnected penetration enhancer containing vesicles (PEVs) are proposed as carriers for dermal delivery of diclofenac. PEVs were prepared by using a commercial phosphatidylcholine mixture (180 mg/m) and transcutol in different amounts. Conventional liposomes were also prepared and tested as control. All vesicles showed a mean size ranging from 75 to 253 nm with fairly narrow size distribution, negative zeta potential value, and drug loading capacity between 48 and 70%. SWAXS studies showed that composition affected vesicle structure and morphology: 10 and 30% transcutol PEVs were unilamellar while liposomes and 20% transcutol PEVs were multilamellar. Rheological studies demonstrated that control liposomes and 10 and 30% transcutol containing PEVs behaved as Newtonian fluids while 20% transcutol containing PEVs showed a plastic behavior. Ex vivo (trans)dermal delivery experiments showed an improved skin deposition of diclofenac when PEVs were used. Vesicle toxicity and uptake of fibroblasts, target of inflammation treatment, were evaluated by MTT test and fluorescence microscopy. Control liposomes and PEVs were both able to interact and being internalized by the 3T3 fibroblasts at all time exposure tested. Furthermore, PEVs showed to be able to reduce the in vitro drug toxicity.
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, University of Cagliari, Cagliari 09124, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, University of Cagliari, Cagliari 09124, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
authors.affiliation: Dept. di Scienze Biomediche, Cittadella Universitaria di Monserrato, Cagliari, Italy.
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Falchi
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, University of Cagliari, Cagliari 09124, Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Castangia
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, University of Cagliari, Cagliari 09124, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Valenti
authors.affiliation: Dept. di Chimica, Cittadella Universitaria di Monserrato, Cagliari, Italy.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Lampis
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, University of Cagliari, Cagliari 09124, Italy. Electronic address: mfadda@unica.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D066298:In Vitro Techniques; D051379:Mice; D016624:Negative Staining; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D010714:Phosphatidylethanolamines / Q000378:metabolism; D012212:Rheology / Q000187:drug effects; D012235:Rhodamines / Q000378:metabolism; D053838:Scattering, Small Angle; D012867:Skin / Q000187:drug effects*; D034421:Sus scrofa; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000633:toxicity; D014961:X-Ray Diffraction
chemical_list: D005452:Fluoresceins; C053685:N-(lissamine rhodamine B sulfonyl)-1,2-dioleoylphosphatidylethanolamine; D010714:Phosphatidylethanolamines; D012235:Rhodamines; D053835:Unilamellar Liposomes; D004008:Diclofenac; C024098:6-carboxyfluorescein
keywords: 3T3 uptake; Cell toxicity; Penetration enhancer; Phospholipid vesicles; Skin delivery