title: A pharmaceutical study of doxorubicin-loaded PEGylated nanoparticles for magnetic drug targeting.
abstract: One of the new strategies to improve cancer chemotherapy is based on new drug delivery systems, like the polyethylene glycol-coated superparamagnetic iron oxide nanoparticles (PEG-SPION, thereafter called PS). In this study, PS are loaded with doxorubicin (DOX) anticancer drug, using a pre-formed DOX-Fe(2+) complex reversible at lower pH of tumour tissues and cancer cells. The DOX loaded PS (DLPS, 3% w/w DOX/iron oxide) present a hydrodynamic size around 60nm and a zeta potential near zero at physiological pH, both parameters being favourable for increased colloidal stability in biological media and decreased elimination by the immune system. At physiological pH of 7.4, 60% of the loaded drug is gradually released from the DLPS in ∼2h. The intracellular release and distribution of DOX is followed by means of confocal spectral imaging (CSI) of the drug fluorescence. The in vitro cytotoxicity of the DLPS on MCF-7 breast cancer cells is equivalent to that of a DOX solution. The reversible association of DOX to the SPION surface and the role of polymer coating on the drug loading/release are discussed, both being critical for the design of novel stealth magnetic nanovectors for chemotherapy.
authors.affiliation: Université François-Rabelais, EA 4244 Physico-Chimie des Matériaux et des Biomolécules, équipe Nanovecteurs Magnétiques pour la Chimiothérapie, Tours F-37200, France.
authors.forename: J
authors.initials: J
authors.lastname: Gautier
authors.forename: E
authors.initials: E
authors.lastname: Munnier
authors.forename: A
authors.initials: A
authors.lastname: Paillard
authors.forename: K
authors.initials: K
authors.lastname: Hervé
authors.forename: L
authors.initials: L
authors.lastname: Douziech-Eyrolles
authors.forename: M
authors.initials: M
authors.lastname: Soucé
authors.forename: P
authors.initials: P
authors.lastname: Dubois
authors.forename: I
authors.initials: I
authors.lastname: Chourpa
mesh_terms: D001682:Biological Availability; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002712:Chlorides / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007526:Isoelectric Point; D008027:Light; D008280:Magnetics / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence / Q000379:methods; D009566:Nitrates / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011437:Propylamines / Q000737:chemistry; D012542:Scattering, Radiation; D012821:Silanes / Q000737:chemistry; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D005296:Ferrous Compounds; D058185:Magnetite Nanoparticles; D009566:Nitrates; D011437:Propylamines; D012821:Silanes; C088294:3-aminopropyltrimethoxysilane; D011092:Polyethylene Glycols; D004317:Doxorubicin; C025302:ferric nitrate; C029451:ferrous chloride; C024555:ferric chloride