Functionalized magnetic nanoparticles as vehicles for the delivery of the antitumor drug gemcitabine to tumor cells. Physicochemical in vitro evaluation

• Published in: Materials Science & Engineering C Vol. 33; no. 3; pp. 1183 - 1192
• Main Authors: Viota, J.L., Carazo, A., Munoz-Gamez, J.A., Rudzka, K., Gómez-Sotomayor, R., Ruiz-Extremera, A., Salmerón, J., Delgado, A.V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2013
• Subjects: Acrylic Resins - chemistry; Adsorption; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Chemical Phenomena; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Deoxycytidine - therapeutic use; Drug Delivery Systems; Electrophoresis; Electrophoretic mobility; Folic Acid - analysis; Gemcitabine; Humans; Hydrogen-Ion Concentration - drug effects; Magnetic nanoparticles; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - ultrastructure; Microscopy, Confocal; Neoplasms - drug therapy; Optical Imaging; Particle Size; Polyelectrolyte coating; Soft particle; Tumor cell; Polyelectrolyte coating; Gemcitabine; Electrophoretic mobility; Soft particle; Tumor cell; Magnetic nanoparticles
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2012.12.009

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.
A. Schematic illustration of the formation of gemcitabine/chitosan/carbopol-coated magnetite nanoparticles. B. Clear field microscopy picture of folic acid/chitosan-coated carbopol–magnetite nano particles inside liver cancer cells. C. Confocal images of human liver tumor cells treated with nanoparticles, after 1h (top), and after 2h (bottom). [Display omitted]
► We describe the synthesis of drug vehicles based on magnetic nanocomposites. ► Electrophoresis and optical absorbance are used to detect gemcitabine loading. ► Release of the antitumor drug into liver, colon and breast tumor cells is proved. ► Vehiculization of the drug improves its cytotoxicity over that of free gemcitabine.