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

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 degradatio...

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Bibliographic Details
Published in:International journal of nanomedicine 2016-01, Vol.11, p.3621-3640
Main Authors: Madureira, Ana Raquel, Nunes, Sara, Campos, Débora A, Fernandes, João C, Marques, Cláudia, Zuzarte, Monica, Gullón, Beatriz, Rodríguez-Alcalá, Luís M, Calhau, Conceição, Sarmento, Bruno, Gomes, Ana Maria, Pintado, Maria Manuela, Reis, Flávio
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Apoptosis
Bioavailability
Cancer
Cell Survival - drug effects
Cinnamates - administration & dosage
Cinnamates - adverse effects
Cinnamates - pharmacology
Cytokinesis - drug effects
Cytotoxicity
Deoxyribonucleic acid
Depsides - administration & dosage
Depsides - adverse effects
Depsides - pharmacology
DNA
DNA - metabolism
Fatty acids
Feces
Food
Functional foods & nutraceuticals
Gastrointestinal Microbiome - drug effects
Lipids
Lipids - chemistry
Lipids - toxicity
Lymphocytes - drug effects
Male
Microbiota
Microbiota (Symbiotic organisms)
Nanomaterials
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - toxicity
Nanoparticles - ultrastructure
Original Research
Oxidation-Reduction
Pharmaceutical industry
Polyphenols
Rats, Wistar
Real-Time Polymerase Chain Reaction
Rosmarinic Acid
Studies
Triglycerides - chemistry
Waxes
Waxes - chemistry
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Summary: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.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S104623