title: A new topical formulation for psoriasis: development of methotrexate-loaded nanostructured lipid carriers.
abstract: The aim of the present work was to develop and assess the potential of nanostructured lipid carriers (NLCs) loaded with methotrexate as a new approach for topical therapy of psoriasis. Methotrexate-loaded NLCs were prepared via a modified hot homogenization combined with ultrasonication techniques using either polysorbate 60 (P60) or 80 (P80) as surfactants. The produced NLCs were within the nanosized range (274-298 nm) with relatively low polydispersity index (<0.25) and zeta potential values around -40 mV. NLCs demonstrated storage stability at 25°C up to 28 days. The entrapment efficiency of methotrexate in NLC-P60 and -P80 was ∼65%. Cryo-SEM images showed the spherical shape of the empty and methotrexate-loaded NLCs. FT-IR confirmed methotrexate presence within the NLCs. The in vitro release of methotrexate from the NLCs followed a fast release pattern reaching ∼70% in 2h. In vitro skin penetration study demonstrated that methotrexate-loaded NLCs-P60 had higher skin penetration when compared to free methotrexate, suggesting a significant role of drug-nanocarriers on topical administration. Methotrexate-loaded NLC-P60 provided drug fluxes of 0.88 μg/cm(2)/h, higher (P<0.001) than with the free drug (control, 0.59 μg/cm(2)/h). The results indicate the potential of NLCs for the delivery of methotrexate to topical therapy of psoriasis.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Maria Filipa
authors.initials: MF
authors.lastname: Pinto
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Catarina Costa
authors.initials: CC
authors.lastname: Moura
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.affiliation: 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: 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: 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: D000279:Administration, Cutaneous; D000818:Animals; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011565:Psoriasis / Q000188:drug therapy*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013499:Surface Properties; D013552:Swine
chemical_list: D003879:Dermatologic Agents; D004337:Drug Carriers; D008055:Lipids; D008727:Methotrexate
keywords: Lipid nanoparticles; Methotrexate; Psoriasis; Skin permeation; Transdermal drug delivery