title: Methotrexate loaded lipid nanoparticles for topical management of skin-related diseases: Design, characterization and skin permeation potential.
abstract: Methotrexate exhibits poor cutaneous bioavailability when administered topically using conventional vehicles. It is recommended for the treatment of skin-related diseases but its systemic side effects hamper application. The aim of this work was to formulate methotrexate in nanostructured lipid carriers using biocompatible lipids, and to investigate their potential for topical drug delivery. Methotrexate-loaded nanostructured lipid carriers were prepared via a hot ultrasonication method. Nanocarriers were evaluated for size, polydispersity, surface potential and entrapment efficiency. Shape and surface morphology of the produced lipid carriers confirmed their spherical shape. After 10h ca. 50% of methotrexate was released in vitro from the lipid nanocarriers following Peppas-Korsmeyer release kinetics. Moreover, methotrexate-loaded nanocarriers were stable at least for 3 months and less toxic towards fibroblasts and human keratinocytes than the free drug. Methotrexate within lipid nanocarriers was able to pass the experimental keratinocyte epidermal barrier at a flux rate of 2μgcm(-2)h(-1). Results demonstrated that lipid nanocarriers constitute a suitable approach for application of methotrexate in skin-related diseases topical therapy.
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Mara
authors.initials: M
authors.lastname: Ferreira
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Silva
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Barreiros
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Segundo
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address: slima@ff.up.pt.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Costa Lima
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D065546:Drug Liberation; D004355:Drug Stability; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry*; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects
chemical_list: D008055:Lipids; D008727:Methotrexate
keywords: Apical-basolateral flux; Biocompatibility; HaCaT keratinocytes monolayer; In vitro drug kinetics release; Nanostructured lipid nanoparticles; Topical drug delivery