Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice

详细信息    查看全文

• 作者：Hé ; loï ; se Ragelle¹ ; Sylvie Crauste-Manciet¹ ; Johanne Seguin ; Denis Brossard ; Daniel Scherman ; Philippe Arnaud ; Guy G. Chabot ; ^{guy.chabot@parisdescartes.fr}
• 关键词：Fisetin ; 3 ; 3&prime ; 4&prime ; 7-tetrahydroxyflavone ; EAhy 926 ; immortalized human umbilical vein endothelial cells ; HLB ; hydrophilic&ndash ; lipophilic balance ; HPLC ; high performance liquid chromatography ; PDI ; polydispersity index
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 出版时间：10 May, 2012
• 年：2012
• 卷：427
• 期：2
• 页码：452-459
• 全文大小：598 K

文摘

The natural flavonoid fisetin (3,3?4?7-tetrahydroxyflavone) has shown antitumour activity but its administration is complicated by its low water solubility. Our aim was to incorporate fisetin into a nanoemulsion to improve its pharmacokinetics and therapeutic efficacy. Solubility and emulsification tests allowed to develop an optimal nanoemulsion composed of Miglyol^? 812N/Labrasol^?/Tween^? 80/Lipoid E80^?/water (10 % /10 % /2.5 % /1.2 % /76.3 % ). The nanoemulsion had an oil droplet diameter of 153 ¡À 2 nm, a negative zeta potential (?8.4 ¡À 0.6 mV) and a polydispersity index of 0.129. The nanoemulsion was stable at 4 ¡ãC for 30 days, but phase separation occurred at 20 ¡ãC. Pharmacokinetic studies in mice revealed that the fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant difference in systemic exposure compared to free fisetin. However, when the fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in fisetin relative bioavailability was noted, compared to free fisetin. Additionally, the antitumour activity of the fisetin nanoemulsion in Lewis lung carcinoma bearing mice occurred at lower doses (36.6 mg/kg) compared to free fisetin (223 mg/kg). In conclusion, we have developed a stable nanoemulsion of fisetin and have shown that it could improve its relative bioavailability and antitumour activity.