title: Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: in vivo and in vitro evaluation.
abstract: OBJECTIVE
  To develop quercetin-loaded phospholipid vesicles, namely liposomes and PEVs (Penetration Enhancer-containing Vesicles), and to investigate their efficacy on TPA-induced skin inflammation.
  
  
  METHODS
  Vesicles were made from a mixture of phospholipids, quercetin and polyethylene glycol 400 (PEG), specifically added to increase drug solubility and penetration through the skin. Vesicle morphology and self-assembly were probed by Cryo-Transmission Electron Microscopy and Small/Wide Angle X-ray Scattering, as well as the main physico-chemical features by Light Scattering. The anti-inflammatory efficacy of quercetin nanovesicles was assessed in vivo on TPA-treated mice dorsal skin by the determination of two biomarkers: oedema formation and myeloperoxidase activity. The uptake of vesicles by 3T3 fibroblasts was also evaluated.
  
  
  RESULTS
  Small spherical vesicles were produced. Their size and lamellarity was strongly influenced by the PEG content (0%, 5%, 10% v/v). The administration of vesicular quercetin on TPA-inflamed skin resulted in an amelioration of the tissue damage, with a noticeable attenuation of oedema and leukocyte infiltration, especially using 5% PEG-PEVs, as also confirmed by confocal microscopy. In vitro studies disclosed a massive uptake and diffusion of PEVs in dermal fibroblasts.
  
  
  CONCLUSIONS
  The proposed approach based on quercetin vesicular formulations may be of value in the treatment of inflammatory skin disorders.
authors.affiliation: Department of Scienze della Vita e dell'Ambiente Sezione di Scienze del Farmaco, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy, caddeoc@unica.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Caddeo
authors.forename: Octavio
authors.initials: O
authors.lastname: Díez-Sales
authors.forename: Ramon
authors.initials: R
authors.lastname: Pons
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernàndez-Busquets
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
mesh_terms: D016475:3T3 Cells; D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008081:Liposomes; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D014961:X-Ray Diffraction
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008081:Liposomes; D011794:Quercetin