title: A novel nanogel formulation of methotrexate for topical treatment of psoriasis: optimization, in vitro and in vivo evaluation.
abstract: BACKGROUND
  Although several formulation strategies have been developed for the treatment of psoriasis, there is an unmet need for optimization of its therapy.
  
  
  OBJECTIVE
  The objective was to develop a nanogel composed of methotrexate (MTX)-loaded nanostructured lipid carrier (MTX-NLC) and to evaluate its potential in imiquimod-induced psoriasis model to ameliorate symptoms of psoriasis.
  
  
  METHODS
  MTX-NLC nanogel was prepared by hot-homogenization method and optimized by Design of Experiments. Particle size, polydispersity index (PDI) and entrapment efficiency were selected as the critical quality attributes. Antipsoriatic potential of MTX-NLC nanogel was evaluated by Psoriatic Area and Severity Index (PASI) score and histopathological examination in the imiquimod-induced psoriasis model.
  
  
  CONCLUSIONS
  Optimized MTX-NLC exhibited particle size of 278 ± 10 nm, PDI of 0.231 ± 0.05 and EE of 22.29 ± 1.23%. At the end of 48 h, MTX-NLC gel exhibited slow and prolonged release of MTX (47.32 ± 0.94% versus 94.23 ± 0.79%) compared to MTX gel. Furthermore, it significantly reduced the PASI score with recovery of normalcy of the mice's skin, while the MTX gel exhibited signs of hyper and parakeratosis at the end of the study.
  
  
  CONCLUSIONS
  The developed MTX-NLC gel formulation can be a promising alternative to existing MTX formulation in treating psoriasis.
authors.affiliation: a National Institute of Pharmaceutical Education and Research (NIPER) , SAS Nagar, (Mohali) , Punjab , India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Avasatthi
authors.affiliation: a National Institute of Pharmaceutical Education and Research (NIPER) , SAS Nagar, (Mohali) , Punjab , India.
authors.forename: Harish
authors.initials: H
authors.lastname: Pawar
authors.affiliation: a National Institute of Pharmaceutical Education and Research (NIPER) , SAS Nagar, (Mohali) , Punjab , India.
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
authors.affiliation: a National Institute of Pharmaceutical Education and Research (NIPER) , SAS Nagar, (Mohali) , Punjab , India.
authors.forename: Prajeet
authors.initials: P
authors.lastname: Bansod
authors.affiliation: a National Institute of Pharmaceutical Education and Research (NIPER) , SAS Nagar, (Mohali) , Punjab , India.
authors.forename: Manjinder Singh
authors.initials: MS
authors.lastname: Gill
authors.affiliation: a National Institute of Pharmaceutical Education and Research (NIPER) , SAS Nagar, (Mohali) , Punjab , India.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D065546:Drug Liberation / Q000187:drug effects / Q000502:physiology; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D008727:Methotrexate
keywords: Imiquimod; methotrexate; nanostructured lipid carriers; psoriasis