title: Functionalized magnetic nanoparticles as vehicles for the delivery of the antitumor drug gemcitabine to tumor cells. Physicochemical in vitro evaluation.
abstract: Gemcitabine is a chemotherapy drug used in different carcinomas, although because it displays a short biological half-life, its plasmatic levels can quickly drop below the effective threshold. Nanoparticle-based drug delivery systems can provide an alternative approach for regulating the bioavailability of this and most other anticancer drugs. In this work we describe a new model of composite nanoparticles consisting of a core of magnetite nanoparticles, coated with successive layers of high molecular weight poly(acrylic acid) and chitosan, and a final layer of folic acid. The possibility of using these self-assembled nanostructures for gemcitabine vehiculization is explored. First, the surface charge of the composite particles is studied by means of electrophoretic mobility measurements as a function of pH for poly(acrylic acid) (carbopol) of different molecular weights. The adsorption of folic acid, aimed at increasing the chances of the particles to pass the cell membrane, is followed up by optical absorbance measurements, which were also employed for drug adsorption determinations. As a main result, it is shown that gemcitabine adsorbs onto the surface of chitosan/carbopol-coated magnetite nanoparticles. In vitro experiments show that the functionalized magnetic nanoparticles are able to deliver the drug to the nuclei of liver, colon and breast tumor cells.
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital Universitario San Cecilio, 18012, Granada, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Viota
authors.forename: A
authors.initials: A
authors.lastname: Carazo
authors.forename: J A
authors.initials: JA
authors.lastname: Munoz-Gamez
authors.forename: K
authors.initials: K
authors.lastname: Rudzka
authors.forename: R
authors.initials: R
authors.lastname: Gómez-Sotomayor
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Extremera
authors.forename: J
authors.initials: J
authors.lastname: Salmerón
authors.forename: A V
authors.initials: AV
authors.lastname: Delgado
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000327:Adsorption; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004586:Electrophoresis; D005492:Folic Acid / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000188:drug therapy*; D061848:Optical Imaging; D010316:Particle Size; D000093542:Gemcitabine
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D003841:Deoxycytidine; C006903:carbopol 940; D005492:Folic Acid; D000093542:Gemcitabine
keywords: Electrophoretic mobility; Gemcitabine; Magnetic nanoparticles; Polyelectrolyte coating; Soft particle; Tumor cell