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

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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.

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REFERENCES

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  10. Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 1990;186:343–55.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  16. Stewart JC. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem. 1980;104:10–4.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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 

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by a grant from the University of Valencia (Relacions Internacionals I Cooperació), a grant from MIUR, Italy (PRIN 2010–2011, Prot. 2010H834LS_004), a grant from the Ministerio de Ciencia e Innovación, Spain (BIO2011-25039), which included FEDER funds, and by a grant from the Generalitat de Catalunya, Spain (2009SGR-760). Dr. C. Caddeo gratefully acknowledges Sardinia Regional Government for the financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007–2013 - Axis IV Human Resources, Objective l.3, Line of Activity l.3.1 “Avviso di chiamata per il finanziamento di Assegni di Ricerca”. Dr. X. Fernàndez-Busquets acknowledges the support of the Cryo-Electron Microscopy Unit at the Scientific and Technological Centres from the University of Barcelona (CCiT-UB).

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Authors and Affiliations

  1. Department of Scienze della Vita e dell’Ambiente Sezione di Scienze del Farmaco, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Carla Caddeo, Anna Maria Fadda & Maria Manconi

  2. Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Avda Vicente Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain

    Octavio Díez-Sales

  3. Instituto de Reconocimiento Molecular y Desarrollo Tecnológico, Centro Mixto Universidad Politécnica de Valencia Universidad de Valencia, Valencia, Spain

    Octavio Díez-Sales

  4. Department of Tecnologia Química i de Tensioactius, Institut de Química Avançada de Catalunya (IQAC-CSIC), 08034, Barcelona, Spain

    Ramon Pons

  5. Nanobioengineering Group, Institute for Bioengineering of Catalonia, Baldiri Reixac 10-12, Barcelona, 08028, Spain

    Xavier Fernàndez-Busquets

  6. Barcelona Centre for International Health Research, CRESIB Hospital Clínic-Universitat de Barcelona, Rosselló 149-153, Barcelona, 08036, Spain

    Xavier Fernàndez-Busquets

  7. Biomolecular Interactions Team Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Martí i Franquès 1, Barcelona, 08028, Spain

    Xavier Fernàndez-Busquets

Authors
  1. Carla Caddeo
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  2. Octavio Díez-Sales
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  3. Ramon Pons
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  4. Xavier Fernàndez-Busquets
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  5. Anna Maria Fadda
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  6. Maria Manconi
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Corresponding author

Correspondence to Carla Caddeo.

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Caddeo, C., Díez-Sales, O., Pons, R. et al. Topical Anti-Inflammatory Potential of Quercetin in Lipid-Based Nanosystems: In Vivo and In Vitro Evaluation. Pharm Res 31, 959–968 (2014). https://doi.org/10.1007/s11095-013-1215-0

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  • DOI: https://doi.org/10.1007/s11095-013-1215-0

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