Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5&...

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Autores principales:	Madureira AR, Nunes S, Campos DA, Fernandes JC, Marques C, Zuzarte M, Gullón B, Rodríguez-Alcalá LM, Calhau C, Sarmento B, Gomes AM, Pintado MM, Reis F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	solid lipid nanoparticles rosmarinic acid witepsol and carnauba waxes safety profile in vitro and animal toxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a739b93bcdb943cab87669f7aaf8be47
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spelling	oai:doaj.org-article:a739b93bcdb943cab87669f7aaf8be472021-12-02T04:52:49ZSafety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches1178-2013https://doaj.org/article/a739b93bcdb943cab87669f7aaf8be472016-08-01T00:00:00Zhttps://www.dovepress.com/safety-profile-of-solid-lipid-nanoparticles-loaded-with-rosmarinic-aci-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5–7 Ana Maria Gomes,1 Maria Manuela Pintado,1 Flávio Reis2 1Catholic University of Portugal, CBQF – Center for Biotechnology and Fine Chemistry – Associate Laboratory, Faculty of Biotechnology, Porto, Portugal; 2Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, and CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal; 3Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal; 4Center for Health Technology and Services Research (CINTESIS), Porto, Portugal; 5Department of Pharmaceutical Sciences, Institute of Health Sciences-North, CESPU, Gandra, Portugal; 6“I3S” Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 7INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal Abstract: Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. Keywords: solid lipid nanoparticles, rosmarinic acid, Witepsol and Carnauba waxes, safety profile, in vitro and animal toxicityMadureira ARNunes SCampos DAFernandes JCMarques CZuzarte MGullón BRodríguez-Alcalá LMCalhau CSarmento BGomes AMPintado MMReis FDove Medical Pressarticlesolid lipid nanoparticlesrosmarinic acidwitepsol and carnauba waxessafety profilein vitro and animal toxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3621-3640 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	solid lipid nanoparticles rosmarinic acid witepsol and carnauba waxes safety profile in vitro and animal toxicity Medicine (General) R5-920
spellingShingle	solid lipid nanoparticles rosmarinic acid witepsol and carnauba waxes safety profile in vitro and animal toxicity Medicine (General) R5-920 Madureira AR Nunes S Campos DA Fernandes JC Marques C Zuzarte M Gullón B Rodríguez-Alcalá LM Calhau C Sarmento B Gomes AM Pintado MM Reis F Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
description	Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5–7 Ana Maria Gomes,1 Maria Manuela Pintado,1 Flávio Reis2 1Catholic University of Portugal, CBQF – Center for Biotechnology and Fine Chemistry – Associate Laboratory, Faculty of Biotechnology, Porto, Portugal; 2Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, and CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal; 3Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal; 4Center for Health Technology and Services Research (CINTESIS), Porto, Portugal; 5Department of Pharmaceutical Sciences, Institute of Health Sciences-North, CESPU, Gandra, Portugal; 6“I3S” Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 7INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal Abstract: Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. Keywords: solid lipid nanoparticles, rosmarinic acid, Witepsol and Carnauba waxes, safety profile, in vitro and animal toxicity
format	article
author	Madureira AR Nunes S Campos DA Fernandes JC Marques C Zuzarte M Gullón B Rodríguez-Alcalá LM Calhau C Sarmento B Gomes AM Pintado MM Reis F
author_facet	Madureira AR Nunes S Campos DA Fernandes JC Marques C Zuzarte M Gullón B Rodríguez-Alcalá LM Calhau C Sarmento B Gomes AM Pintado MM Reis F
author_sort	Madureira AR
title	Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
title_short	Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
title_full	Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
title_fullStr	Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
title_full_unstemmed	Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
title_sort	safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/a739b93bcdb943cab87669f7aaf8be47
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Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

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