title: Pure antiestrogen RU 58668-loaded nanospheres: morphology, cell activity and toxicity studies.
abstract: Nanospheres (NS) formulated using biodegradable and biocompatible polymers, poly(D,L-lactide-co-glycolide) (PLGA), poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL), loaded with the pure anti-estrogen RU 58668 (RU), a promising estrogen-dependent anticancer agent, have been prepared. They all possess a small size compatible with an intratumoral extravasation behavior and their pegylation reduce significantly their zeta potential. Characterization by freeze fracture electron microscopy have shown that NS are spheric particles with a size ranging between 30 and 50nm and a tendency to agglomerate which is reduced by polyethylene glycol (PEG) grafting. PEG-grafted NS are all non-toxic as revealed by cell viability assay. A specific cellular model has been used to evaluate not only the release extent of the drug but also its biological activity. All formulations tested showed that they release slowly RU as measured by the delayed ability of RU to inhibit estrogen-induced transcription in human breast cancer cells and that they possess only a small amount of surface adsorbed RU.
authors.affiliation: UMR CNRS 8612, Pharmacologie Cellulaire et Moléculaire, 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France. michael.renoir@cep.u-psud.fr
authors.forename: Thibault
authors.initials: T
authors.lastname: Ameller
authors.forename: Véronique
authors.initials: V
authors.lastname: Marsaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Legrand
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.forename: Jack Michel
authors.initials: JM
authors.lastname: Renoir
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004337:Drug Carriers; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000633:toxicity; D008156:Luciferases / Q000235:genetics; D008854:Microscopy, Electron; D008954:Models, Biological; D036103:Nanotechnology; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000633:toxicity; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D005466:Fluorocarbons
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D019344:Lactic Acid; D008156:Luciferases; D011091:Polyesters; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; C086511:RU 58668; D005466:Fluorocarbons; C016240:polycaprolactone; C033616:poly(lactide)