Pharmaceutical Research

, Volume 31, Issue 4, pp 959–968 | Cite as

Topical Anti-Inflammatory Potential of Quercetin in Lipid-Based Nanosystems: In Vivo and In Vitro Evaluation

  • Carla Caddeo
  • Octavio Díez-Sales
  • Ramon Pons
  • Xavier Fernàndez-Busquets
  • Anna Maria Fadda
  • Maria Manconi
Research Paper

ABSTRACT

Purpose

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.

KEY WORDS

dermal fibroblasts mice quercetin skin inflammation vesicles 

REFERENCES

  1. 1.
    Caddeo C, Teskač K, Sinico C, Kristl J. Effect of resveratrol incorporated in liposomes on proliferation and UV-B protection of cells. Int J Pharm. 2008;363:183–91.PubMedCrossRefGoogle Scholar
  2. 2.
    Caddeo C, Manconi M, Fadda AM, Lai F, Lampis S, Diez-Sales O, et al. Nanocarriers for antioxidant resveratrol: formulation approach, vesicle self-assembly and stability evaluation. Colloid Surf B-Biointerfaces. 2013;111:327–32.CrossRefGoogle Scholar
  3. 3.
    Pando D, Caddeo C, Manconi M, Fadda AM, Pazos C. Nanodesign of olein vesicles for the topical delivery of the antioxidant resveratrol. J Pharm Pharmacol. 2013;65:1158–67.Google Scholar
  4. 4.
    Chessa M, Caddeo C, Valenti D, Manconi M, Sinico C, Fadda AM. Effect of penetration enhancer containing vesicles on the percutaneous delivery of quercetin through new born pig skin. Pharmaceutics. 2011;3:497–509.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Date AA, Nagarsenker MS, Patere S, Dhawan V, Gude RP, Hassan PA, et al. Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration. Mol Pharm. 2011;8:716–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Vicentini FTMC, Fonseca YM, Pitol DL, Iyomasa MM, Bentley MVLB, Fonseca MJV. Evaluation of protective effect of a water-in-oil microemulsion incorporating quercetin against UVB-induced damage in hairless mice skin. J Pharm Pharm Sci. 2010;13:274–85.PubMedGoogle Scholar
  7. 7.
    Wagner C, Vargas AP, Roos DH, Morel AF, Farina M, Nogueira CW, et al. Comparative study of quercetin and its two glycoside derivatives quercetin and rutin against methylmercury (MgHg)-induced ROS production in rat brain slices. Arch Toxicol. 2010;84:89–97.PubMedCrossRefGoogle Scholar
  8. 8.
    Chen-yu G, Chun-fen Y, Qi-lu L, Qi T, Yan-wei X, Wei-na L, et al. Development of a quercetin-loaded nanostructured lipid carrier formulation for topical delivery. Int J Pharm. 2012;430:292–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Bose S, Du Y, Takhistov P, Michniak-Kohn B. Formulation optimization and topical delivery of quercetin from solid lipid based nanosystems. Int J Pharm. 2013;441:56–66.PubMedCrossRefGoogle Scholar
  10. 10.
    Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 1990;186:343–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Saija A, Scalese M, Lanza M, Marzullo D, Bonina F, Castelli F. Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radical Biol Med. 1995;19:481–6.CrossRefGoogle Scholar
  12. 12.
    Tan Q, Liu W, Guo C, Zhai G. Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. Int J Nanomed. 2011;6:1621–30.CrossRefGoogle Scholar
  13. 13.
    Montenegro L, Carbone C, Maniscalco C, Lambusta D, Nicolosi G, Ventura CA, et al. In vitro evaluation of quercetin-3-O-acyl esters as topical prodrugs. Int J Pharm. 2007;336:257–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Censi R, Martena V, Hoti E, Malaj L, Di MP. Permeation and skin retention of quercetin from microemulsions containing Transcutol® P. Drug Dev Ind Pharm. 2012;38:1128–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Cadena PG, Pereira MA, Cordeiro RBS, Cavalcanti IMF, Barros Neto B, Pimentel Mdo C, et al. Nanoencapsulation of quercetin and resveratrol into elastic liposomes. Biochim Biophys Acta. 2013;1828:309–16.PubMedCrossRefGoogle Scholar
  16. 16.
    Stewart JC. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem. 1980;104:10–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Pabst G, Rappolt M, Amenitsch H, Laggner P. Structural information from multilamellar liposomes at full hydration: full q-range fitting with high quality x-ray data. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000;62:4000–9.PubMedGoogle Scholar
  18. 18.
    De Vry CG, Valdez M, Lazarov M, Muhr E, Buelow R, Fong T, et al. Topical application of a novel immunomodulatory peptide, RDP58, reduces skin inflammation in the phorbol ester-induced dermatitis model. J Invest Dermatol. 2005;125:473–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Caddeo C, Diez Sales O, Valenti D, Ruiz Saurí A, Fadda AM, Manconi M. Inhibition of skin inflammation in mice by diclofenac in vesicular carriers: liposomes, ethosomes and PEVs. Int J Pharm. 2013;443:128–36.PubMedCrossRefGoogle Scholar
  20. 20.
    De Young LM, Kheifets JB, Ballaron SJ, Young JM. Edema and cell infiltration in the phorbol ester-treated mouse ear aretemporally separate and can be differentially modulated by pharmacologic agents. Agents Actions. 1989;26:335–41.PubMedCrossRefGoogle Scholar
  21. 21.
    Sato H, Nakayama Y, Yamashita C, Uno H. Anti-inflammatory effects of tacalcitol (1,24(R)(OH)2D3, TV-02) in the skin of TPA-treated hairless mice. J Dermatol. 2004;31:200–17.PubMedGoogle Scholar
  22. 22.
    Manconi M, Sinico C, Caddeo C, Vila AO, Valenti D, Fadda AM. Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin. Int J Pharm. 2011;412:37–46.PubMedCrossRefGoogle Scholar
  23. 23.
    Manconi M, Caddeo C, Sinico C, Valenti D, Mostallino MC, Lampis S, et al. Penetration enhancer-containing vesicles: composition dependence of structural features and skin penetration ability. Eur J Pharm Biopharm. 2012;82:352–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Caddeo C, Manconi M, Valenti D, Maccioni AM, Fadda AM, Sinico C. The role of Labrasol® in the enhancement of the cutaneous bioavailability of minoxidil in phospholipid vesicles. Res J Pharm Technol. 2012;5:1563–9.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Carla Caddeo
    • 1
  • Octavio Díez-Sales
    • 2
    • 3
  • Ramon Pons
    • 4
  • Xavier Fernàndez-Busquets
    • 5
    • 6
    • 7
  • Anna Maria Fadda
    • 1
  • Maria Manconi
    • 1
  1. 1.Department of Scienze della Vita e dell’Ambiente Sezione di Scienze del FarmacoUniversity of CagliariCagliariItaly
  2. 2.Department of Pharmacy and Pharmaceutical TechnologyUniversity of ValenciaBurjassotSpain
  3. 3.Instituto de Reconocimiento Molecular y Desarrollo TecnológicoCentro Mixto Universidad Politécnica de Valencia Universidad de ValenciaValenciaSpain
  4. 4.Department of Tecnologia Química i de TensioactiusInstitut de Química Avançada de Catalunya (IQAC-CSIC)BarcelonaSpain
  5. 5.Nanobioengineering GroupInstitute for Bioengineering of CataloniaBarcelonaSpain
  6. 6.Barcelona Centre for International Health ResearchCRESIB Hospital Clínic-Universitat de BarcelonaBarcelonaSpain
  7. 7.Biomolecular Interactions Team Nanoscience and Nanotechnology Institute (IN2UB)University of BarcelonaBarcelonaSpain

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