title: Optimization of nanostructured lipid carriers loaded with methotrexate: A tool for inflammatory and cancer therapy.
abstract: The aim of this study was to optimize and assess the potential of nanostructured lipid carriers (NLC), prepared by the hot ultrasonication method, as carrier for methotrexate (MTX), highlighting the application of factorial design. Preliminary screening drug/lipid solubility, allowed us to select Witepsol(®) E85 as the solid lipid and Mygliol(®) 812 as liquid lipid for the NLC loaded with MTX. Then, a 3-level, 3-factor Box-Behnken design and validated by ANOVA analysis; the correspondence between the predicted values and those measured experimentally confirmed the robustness of the design. Properties of optimized MTX-loaded NLCs such as morphology, size, zeta potential, entrapment efficiency, storage stability, in vitro drug release and cytotoxicity were investigated. NLCs loaded with MTX exhibited spherical shape with 252-nm, a polydispersity of 0.06±0.02, zeta potential of -14 mV and an entrapment efficiency of 87%. In vitro release studies revealed a fast initial release followed by a prolonged release of MTX from the NLC up to 24-h. The release kinetics of the optimized NLC best fitted the Peppas-Korsmeyer model for physiological and inflammatory environments and the Hixson-Crowell model skin simulation conditions. No toxicity was observed in fibroblasts. Thus, the optimized MTX-loaded NLC have the potential to be exploited as delivery system.
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Portugal; Faculty of Engineering of University of Porto, Portugal.
authors.forename: Mara
authors.initials: M
authors.lastname: Ferreira
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Portugal.
authors.forename: Luíse L
authors.initials: LL
authors.lastname: Chaves
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Portugal. Electronic address: slima@ff.up.pt.
authors.forename: Sofia A Costa
authors.initials: SA
authors.lastname: Lima
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Portugal.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D004355:Drug Stability; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D014280:Triglycerides; C009683:witepsol; C022834:miglyol 812; D008727:Methotrexate
keywords: Box–Behnken design; Hot ultrasonication; In vitro drug release; L929 fibroblasts; Lipid colloidal carriers; Methotrexate; Mygliol(®) 812; Storage stability; Witepsol(®) E85