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Anti-inflammatory Effect and Toxicology Analysis of Oral Delivery Quercetin Nanosized Emulsion in Rats

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ABSTRACT

Purpose

This study evaluates the advantage of the quercetin encapsulation in nanosized emulsion (QU-NE) administered orally in rats in order to demonstrate its anti-oedematous and antioxidant effects as well as its toxicity.

Methods

The nanocarriers were prepared using the hot solvent diffusion with the phase inversion temperature methods. The nanocarriers physicochemical properties were then investigated. The anti-edematous activity was tested using paw edema in rats. In addition, NF-kB expression in subcutaneous tissue of the paws was accessed by immunohistochemistry while the lipid peroxidation was analyzed in the liver by malondialdehyde reaction with thiobarbituric acid. Hematological, renal and hepatic toxicity as well as the genetic damage were also evaluated.

Results

The results demonstrated that QU-NE exhibited pronounced anti-oedematous property comparable to drug diclofenac. This effect was associated with NF-κB pathway inhibition. The lipid peroxidation was also only reduced in rats treated with QU-NE. Besides this, no genetic damage, hematological, renal or hepatic toxicities were observed after administration of QU-NE.

Conclusions

These results suggest that quercetin nanosized emulsion exhibits anti-oedematous and antioxidant properties and does not demonstrate toxic effects. This indicates that it has a potential application in the treatment of inflammatory diseases.

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Abbreviations

ALT:

Alanine-aminotransferase

AST:

Aspartate-aminotransferase

CMC:

Carboxymethylcellulose

CO:

Castor oil

HBSS:

Hank’s balanced salt solution

HEPES:

Sodium 4-(2-hydroxyethyl)-1-piperazineethanesulfonate

HPLC:

High pressure liquid chromatography

LY:

Metoprolol tartrate and lucifer yellow

MDA:

Malondialdehyde

MES:

Methanesulfonic acid

MN:

Micronucleus

NCEs:

Normochromatic erythrocytes

NE:

Unloaded nanosized emulsion

NSAID:

Nonsteroidal anti-inflammatory drug

PAPP :

Intestinal permeability coefficients

PCEs:

Polychromatic erythrocytes

PDI:

Polydispersed index

PEG 660-stearate:

12-hydroxystearic acid–polyethylene glycol copolymer

PIT:

Phase inversion technique

QU:

Quercetin

QU-NE:

Quercetin nanosized emulsion

QU-SUSP:

Free quercetin

ROS:

Reactive oxygen species

TEER:

Transepithelial electrical resistance

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors are grateful to CNPq for the financial support to the project Casadinho/PROCAD under proposal 552457/2011-6, Fundação de Apoio a Pesquisa do Estado de Minas Gerais and Rede de Pesquisa em Doenças Infecciosas Humanas e Animais do Estado de Minas Gerais. G. Hadrich received grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Laboratório de Nanotecnologia Aplicada à Saúde, Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Rio Grande (FURG), Av Itália, Km 8, Rio Grande, RS, 96210-900,, Brazil

    Gabriela Hädrich, Gustavo Richter Vaz, Michelle Maidana, Flávio Manoel Rodrigues da Silva Jr, Ana Luiza Muccillo-Baisch & Cristiana Lima Dora

  2. Laboratório de Ensaios Farmacológicos e Toxicológicos, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande (FURG), Rio Grande, RS, 96210-900,, Brazil

    Gabriela Hädrich, Flávio Manoel Rodrigues da Silva Jr & Ana Luiza Muccillo-Baisch

  3. Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Florianópolis, SC, 88040-900,, Brazil

    Jadel Muller Kratz

  4. Laboratório de Farmacotécnica, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Bloco K, sala 107, Florianópolis, SC, 88040-900, Brazil

    Gecioni Loch-Neckel

  5. Laboratório de Imunofarmacologia experimental, Departamento de Clínica Médica, Universidade Federal do Triângulo Mineiro, Uberaba, MG, 38025-350,, Brazil

    Daniely Cornélio Favarin & Alexandre de Paula Rogerio

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  1. Gabriela Hädrich
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  2. Gustavo Richter Vaz
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  3. Michelle Maidana
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Correspondence to Cristiana Lima Dora.

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Hädrich, G., Vaz, G.R., Maidana, M. et al. Anti-inflammatory Effect and Toxicology Analysis of Oral Delivery Quercetin Nanosized Emulsion in Rats. Pharm Res 33, 983–993 (2016). https://doi.org/10.1007/s11095-015-1844-6

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