TY - JOUR
T1 - Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use
T2 - in vitro and animal approaches
AU - Madureira, Ana Raquel
AU - Nunes, Sara
AU - Campos, Débora A.
AU - Fernandes, João C.
AU - Marques, Cláudia
AU - Zuzarte, Monica
AU - Gullón, Beatriz
AU - Rodríguez-Alcalá, Luís M.
AU - Calhau, Conceição
AU - Sarmento, Bruno
AU - Gomes, Ana Maria
AU - Pintado, Maria Manuela
AU - Reis, Flávio
PY - 2016/8/4
Y1 - 2016/8/4
N2 - 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.
AB - 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.
KW - In vitro and animal toxicity
KW - Rosmarinic acid
KW - Safety profile
KW - Solid lipid nanoparticles
KW - Witepsol and Carnauba waxes
UR - http://www.scopus.com/inward/record.url?scp=84982730509&partnerID=8YFLogxK
U2 - 10.2147/IJN.S104623
DO - 10.2147/IJN.S104623
M3 - Article
C2 - 27536103
AN - SCOPUS:84982730509
SN - 1176-9114
VL - 11
SP - 3621
EP - 3640
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
ER -