期刊
PHARMACEUTICAL RESEARCH
卷 31, 期 4, 页码 959-968出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-013-1215-0
关键词
dermal fibroblasts; mice; quercetin; skin inflammation; vesicles
资金
- University of Valencia (Relacions Internacionals I Cooperacio)
- MIUR, Italy [Prot. 2010H834LS_004]
- Ministerio de Ciencia e Innovacion, Spain [BIO2011-25039]
- FEDER funds
- Generalitat de Catalunya, Spain [2009SGR-760]
- Sardinia Regional Government [1.3, 1.3.1]
- Cryo-Electron Microscopy Unit at the Scientific and Technological Centres from the University of Barcelona (CCiT-UB)
To develop quercetin-loaded phospholipid vesicles, namely liposomes and PEVs (Penetration Enhancer-containing Vesicles), and to investigate their efficacy on TPA-induced skin inflammation. 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. 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. The proposed approach based on quercetin vesicular formulations may be of value in the treatment of inflammatory skin disorders.
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