title: Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacy.
abstract: 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.
authors: Paris Descartes University, Faculty of Pharmacy, INSERM U1022, CNRS UMR8151, Sorbonne Paris Cité, Chimie ParisTech, Chemical, Genetic & Imaging Pharmacology Laboratory, F-75006 Paris, France.
authors: Johanne
authors: J
authors: Seguin
authors: Laura
authors: L
authors: Brullé
authors: Renaud
authors: R
authors: Boyer
authors: Yen Mei
authors: YM
authors: Lu
authors: Miriam
authors: M
authors: Ramos Romano
authors: Yasmine S
authors: YS
authors: Touil
authors: Daniel
authors: D
authors: Scherman
authors: Michel
authors: M
authors: Bessodes
authors: Nathalie
authors: N
authors: Mignet
authors: Guy G
authors: GG
authors: Chabot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D044948:Flavonols; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D044948:Flavonols; D008081:Liposomes; D003520:Cyclophosphamide; C017875:fisetin