非西汀
生物利用度
药理学
脂质体
类黄酮
化学
体内
刘易斯肺癌
医学
生物化学
抗氧化剂
生物
癌症
内科学
生物技术
转移
作者
Johanne Séguin,Laura Brullé,Renaud Boyer,Yen Mei Lu,Miriam Romano,Yasmine Touil,Daniel Scherman,Michel Bessodes,Nathalie Mignet,Guy G. Chabot
标识
DOI:10.1016/j.ijpharm.2013.01.050
摘要
The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown antiangiogenic and anticancer properties. Because of fisetin limited water solubility, we designed a liposomal formulation and evaluated its biological properties in vitro and in Lewis lung carcinoma (LLC) bearing mice. A liposomal formulation was developed with DOPC and DODA-PEG2000, possessing a diameter in the nanometer range (173.5±2.4nm), a high homogeneity (polydispersity index 0.181±0.016) and high fisetin encapsulation (58%). Liposomal fisetin incubated with LLC cells were internalized, induced a typical fisetin morphological effect and increased the sub-G1 cell distribution. In vivo, liposomal fisetin allowed a 47-fold increase in relative bioavailability compared to free fisetin. The effect of liposomal fisetin on LLC tumor growth in mice at low dose (21mg/kg) allowed a higher tumor growth delay (3.3 days) compared to free fisetin at the same dose (1.6 day). Optimization of liposomal fisetin therapy was attempted by co-treatment with cyclophosphamide which led to a significant improvement in tumor growth delay (7.2 days) compared to cyclophosphamide with control liposomes (4.2 days). In conclusion, fisetin liposomes markedly improved fisetin bioavailability and anticancer efficacy in mice and this formulation could facilitate the administration of this flavonoid in the clinical setting.
科研通智能强力驱动
Strongly Powered by AbleSci AI