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Topical Delivery of Coumestrol from Lipid Nanoemulsions Thickened with Hydroxyethylcellulose for Antiherpes Treatment

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Abstract

We have recently shown that coumestrol, an isoflavonoid-like compound naturally occurring in soybeans, alfafa, and red clover, inhibited Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) replication. In this study, we designed coumestrol formulations in an attempt to enable its topical delivery to mucosa tissues. Physicochemical and microscopic examinations suggested that coumestrol was efficiently incorporated in positively-charged nanoemulsions dispersed in a hydroxyethylcellulose gel. The higher coumestrol flux through excised porcine esophageal mucosa was detected from nanoemulsions composed by a fluid phospholipid (dioleylphosphocholine, DOPC) in comparison with that of a rigid one (distearoylphosphocholine, DSPC) in two mucosa conditions (intact and injured). Such results were supported by confocal fluorescence images. Furthermore, the low IC50 values demonstrated an increasement in the antiviral inhibition against HSV-1 and HSV-2 after incorporation of coumestrol into nanoemulsions containing DOPC. Overall, coumestrol-loaded nanoemulsions proved to be beneficial for herpes simplex treatment.

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ACKNOWLEDGEMENTS

The authors wish to thank the financial support of the National Council for Scientific and Technological Development (CNPq, grant number 459619/2014-4) and the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES, Nanobiotec Network, grant number 902/2009). L.K., V.B., C.M.O.S., and H.T are recipients of CNPq research fellowships.

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Authors and Affiliations

  1. Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, 90610-000, Brazil

    Débora Fretes Argenta, Juliana Bidone, Letícia Scherer Koester, Valquíria Link Bassani & Helder Ferreira Teixeira

  2. Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florianópolis, 88040-970, Brazil

    Cláudia Maria Oliveira Simões

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  1. Débora Fretes Argenta
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  2. Juliana Bidone
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  3. Letícia Scherer Koester
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  4. Cláudia Maria Oliveira Simões
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  5. Helder Ferreira Teixeira
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Correspondence to Helder Ferreira Teixeira.

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Argenta, D.F., Bidone, J., Koester, L.S. et al. Topical Delivery of Coumestrol from Lipid Nanoemulsions Thickened with Hydroxyethylcellulose for Antiherpes Treatment. AAPS PharmSciTech 19, 192–200 (2018). https://doi.org/10.1208/s12249-017-0828-8

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  • DOI: https://doi.org/10.1208/s12249-017-0828-8

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