title: Oral Delivery of a High Quercetin Payload Nanosized Emulsion: In Vitro and In Vivo Activity Against B16-F10 Melanoma.
abstract: Quercetin is a natural compound that has several biological activities including anticancer activity. However, the use of this drug has been limited mostly because of its poor water solubility and low bioavailability. Therefore, the development of quercetin-loaded nanocarrier systems may be considered a promising advance to exploit its therapeutic properties in clinical setting including cancer treatment. This study evaluates the effect of orally administered nanosized emulsion containing quercetin (QU-NE) on the cytotoxicity activity against B16-F10 cells in vitro, and on subcutaneous melanoma in mice inoculated with B16-F1O cells. In vivo experiments, also evaluate the co-administration of quercetin with cisplatin in order to predict synergic effects and the renal and hepatic toxicity. The nanocarriers were prepared through the hot solvent diffusion associated with the phase inversion temperature methods. In vitro study showed reduction of cell viability in a concentration-depend manner for free quercetin and QU-NE. In vivo study, quercetin either as a free drug or colloidal dispersion was administrated at a dose of 5 mg kg(-1) twice a week for 17 days via oral route. Cisplatin was administrated at dose of 1 mg kg(-1) once a week intraperitoneally. Free quercetin and QU-NE reduced tumor growth, however, the reduction observed for QU-NE (P < 0.001 vs. control) was significantly higher than free quercetin (P < 0.05 vs. control). The association of both drugs did not show synergic effect. Besides, no renal or hepatic toxicities were observed after administration of free quercetin and QU-NE. These results suggest that an improvement in the oral bioavailability of quercetin occurred when this compound was dissolved in the oily phase of a nanosized emulsion, indicating that it might have a potential application in the treatment of melanoma.
authors.forename: Cristiana Lima
authors.initials: CL
authors.lastname: Dora
authors.forename: Luis Felipe Costa
authors.initials: LF
authors.lastname: Silva
authors.forename: Leticia
authors.initials: L
authors.lastname: Mazzarino
authors.forename: Jarbas Mota
authors.initials: JM
authors.lastname: Siqueira
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernandes
authors.forename: Leticia Kramer
authors.initials: LK
authors.lastname: Pacheco
authors.forename: Mariana Franzoni
authors.initials: MF
authors.lastname: Maioral
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Santos-Silva
authors.forename: Ana Luiza Muccillo
authors.initials: AL
authors.lastname: Baischl
authors.forename: Jamil
authors.initials: J
authors.lastname: Assreuy
authors.forename: Elenara
authors.initials: E
authors.lastname: Lemos-Senna
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004655:Emulsions; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004655:Emulsions; D011794:Quercetin; D002945:Cisplatin