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

2016Journal article Open access
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dc.contributor.authorReis, Flávio
dc.contributor.authorMadureira, Ana Raquel
dc.contributor.authorNunes, Sara
dc.contributor.authorCampos, Débora
dc.contributor.authorFernandes, João
dc.contributor.authorMarques, Cláudia
dc.contributor.authorZuzarte, Monica
dc.contributor.authorGullón, Beatriz
dc.contributor.authorRodríguez-Alcalá, Luis M.
dc.contributor.authorCalhau, Conceição
dc.contributor.authorSarmento, Bruno
dc.contributor.authorGomes, Ana M.
dc.contributor.authorPintado, M. E.
dc.date.accessioned2017-10-13T18:11:00Z
dc.date.available2017-10-13T18:11:00Z
dc.date.issued2016
dc.description.abstractRosmarinic 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMADUREIRA, Ana Raquel; NUNES, Sara; CAMPOS, Débora; FERNANDES, João C.; MARQUES, Cláudia; ZUZARTE, Monica; GULLÓN, Beatriz; RODRÍGUEZ-ALCALÁ, Luís M.; CALHAU, Conceição; SARMENTO, Bruno; GOMES, Ana M.; PINTADO, M. E.; REIS, Flávio - Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: In vitro and animal approaches. International Journal of Nanomedicine. ISSN 1178-2013. Vol. 11 (2016), p. 3621-3640pt_PT
dc.identifier.doi10.2147/IJN.S104623pt_PT
dc.identifier.eid84982730509
dc.identifier.pmcPMC4977102
dc.identifier.pmid27536103
dc.identifier.urihttp://hdl.handle.net/10400.14/23085
dc.identifier.wos000380739900001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationSAESCTN-PIIC&DT/2011pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectSolid lipid nanoparticlespt_PT
dc.subjectRosmarinic acidpt_PT
dc.subjectWitepsol and Carnauba waxespt_PT
dc.subjectSafety profilept_PT
dc.subjectIn vitro and animal toxicitypt_PT
dc.titleSafety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approachespt_PT
dc.typejournal article
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oaire.citation.endPage3640
oaire.citation.startPage3621
oaire.citation.titleInternational Journal of Nanomedicinept_PT
oaire.citation.volume11
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