Dora Cristiana Lima, Silva Luis Felipe Costa, Mazzarino Leticia, Siqueira Jarbas Mota, Fernandes Daniel, Pacheco Leticia Kramer, Maioral Mariana Franzoni, Santos-Silva Maria Claudia, Baischl Ana Luiza Muccillo, Assreuy Jamil, Lemos-Senna Elenara
J Nanosci Nanotechnol. 2016 Feb;16(2):1275-81. doi: 10.1166/jnn.2016.11675.
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.
槲皮素是一种具有多种生物活性（包括抗癌活性）的天然化合物。然而，这种药物的应用大多受到限制，主要原因是其水溶性差和生物利用度低。因此，开发载槲皮素纳米载体系统可能被认为是在临床环境（包括癌症治疗）中利用其治疗特性的一项有前景的进展。本研究评估口服含槲皮素的纳米乳剂（QU-NE）对体外B16-F10细胞的细胞毒性活性以及对接种B16-F1O细胞的小鼠皮下黑色素瘤的影响。体内实验还评估了槲皮素与顺铂联合给药，以预测协同作用以及肾毒性和肝毒性。通过与相转变温度法相关的热溶剂扩散制备纳米载体。体外研究表明，游离槲皮素和QU-NE以浓度依赖性方式降低细胞活力。在体内研究中，游离药物形式或胶体分散形式的槲皮素通过口服途径以5 mg kg(-1)的剂量每周给药两次，持续17天。顺铂以1 mg kg(-1)的剂量每周腹腔注射一次。游离槲皮素和QU-NE均可降低肿瘤生长，然而，观察到的QU-NE的降低（与对照组相比，P < 0.001）明显高于游离槲皮素（与对照组相比，P < 0.05）。两种药物联合使用未显示协同作用。此外，在给予游离槲皮素和QU-NE后未观察到肾毒性或肝毒性。这些结果表明，当槲皮素溶解在纳米乳剂的油相中时，其口服生物利用度得到了提高，这表明它在黑色素瘤治疗中可能具有潜在应用。
