title: Development of a liposomal formulation of the natural flavonoid fisetin.
abstract: The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been shown to possess antiangiogenic and anticancer properties. Because of the limited water solubility of fisetin, our aim was to design and optimize a liposomal formulation that could facilitate its in vivo administration, taking into account the availability and cost of the various components. Several methods were evaluated such as probe sonication, homogeneization, film hydration and lipid cake formation. A selection of lipid and lipid-PEG was also performed via their incorporation in different formulations based on the size of the liposomes, their polydispersity index (PDI) and the fisetin encapsulation yield. An optimal liposomal formulation was developed with P90G and DODA-GLY-PEG2000, possessing a diameter in the nanometer scale (175nm), a high homogeneity (PDI 0.12) and a high fisetin encapsulation (73%). Fisetin liposomes were stable over 59 days for their particle diameter and still retained 80% of their original fisetin content on day 32. Moreover, liposomal fisetin retained the cytotoxicity and typical morphological effect of free fisetin in different tumour and endothelial cell lines. In conclusion, based on its physico-chemical properties and retention of fisetin biological effects, the developed liposomal fisetin preparation is therefore suitable for in vivo administration.
authors.affiliation: Paris Descartes University, Faculty of Pharmacy, INSERM U1022, CNRS UMR8151, Chimie ParisTech, Chemical, Genetic and Imaging Pharmacology Laboratory (INSERM U1022, CNRS UMR 8151), 4 avenue de l'Observatoire, F-75006 Paris, France. nathalie.mignet@parisdescartes.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mignet
authors.forename: Johanne
authors.initials: J
authors.lastname: Seguin
authors.forename: Miriam
authors.initials: M
authors.lastname: Ramos Romano
authors.forename: Laura
authors.initials: L
authors.lastname: Brullé
authors.forename: Yasmine S
authors.initials: YS
authors.lastname: Touil
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Michel
authors.initials: M
authors.lastname: Bessodes
authors.forename: Guy G
authors.initials: GG
authors.lastname: Chabot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000737:chemistry; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004355:Drug Stability; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D044948:Flavonols; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D004337:Drug Carriers; D005419:Flavonoids; D044948:Flavonols; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D053835:Unilamellar Liposomes; D011092:Polyethylene Glycols; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine; C017875:fisetin