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

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.

Organoclay particles as reinforcing agents in polysaccharide films.

In this work an investigation is described on the use of organically modified montmorillonite clay particles as stabilizers of bioplastic films based on xylan. With the aim of facilitating the incorporation of the nanoparticles to the films, the former were treated with a non-ionic surfactant, inulin. In order to evaluate the possible role of electrostatic interactions in the formation of montmorillonite/xylan complexes, an exhaustive electrokinetic characterization of the modified montmorillonite was carried out. Because montmorillonite has been modified by adsorption of the cationic surfactant DSDMAC, the electrophoretic mobility of montmorillonite in the absence of inulin is positive in a wide range of concentration of NaCl and CaCl(2). On the contrary, addition of KBr provokes a charge inversion when the salt concentration is around 0.05 M, suggesting adsorption of Br(-) ions. In the presence of inulin, the positive electrophoretic mobility decreases with the concentration of this surfactant, and this can be explained by assuming that inulin adsorption is accompanied by simultaneous DSDMAC desorption, eventually producing charge inversion, particularly in the presence of bromide ions. A thorough characterization of the wettability of the xylan films demonstrated that it is dominated by acid-base interactions and that incorporation of inulin-coated montmorillonite leads to a considerable reduction of the hydrophilic character of the films.

Electrokinetic characterization of magnetite nanoparticles functionalized with amino acids.

The synthesis of nanoparticles consisting of a magnetite core coated with one or more layers of amino acid (L-arginine, L-lysine, glycine, and L-glutamine) is described in this paper. For all the amino acids it is found that adsorption increases with concentration in solution in the range 0.5-10 mg/mL. The adsorption, however, differs substantially from one amino acid to another, depending on the length of the hydrocarbon chain and the polarity and charge of the side group. Thus, for given concentration and pH, adsorption is found to increase in the order L-arginine < L-lysine < L-glutamine < glycine. This order corresponds roughly to amino acids with decreasing chain length; in addition, the presence of the less polarizable guanidine group in the arginine molecule may explain why this amino acid is slightly less adsorbed than lysine. The pH dependence of the adsorption of each amino acid is reasonably explained considering the surface charge of magnetite and the charge of the amino acid molecules for different pHs, indicating a significant role of electrostatics in adsorption. This is further checked by means of determinations of the electrophoretic mobility of amino acid-coated magnetite as a function of pH: the results indicate a shift of the isoelectric point of the raw magnetite toward more basic pHs, an indication of adsorption of positive species, as confirmed by the tendency of the mobility of amino acid-coated magnetite toward more positive values below neutral pH. The electrophoretic mobility of coated particles was also measured as a function of the concentration of amino acid, and it was found that for low concentrations the four amino acids provoke charge inversion and overcharging of the magnetite surface at pH 6. Finally, the dependence of the electrophoretic mobility on the ionic strength indicated that from an electrophoretic point of view, the functionalized magnetite-amino acid particles do not behave as soft particles, and that the amino acid coating should be very compact.

Study of the magnetorheology of aqueous suspensions of extremely bimodal magnetite particles.

In this paper we describe the magnetorheological behavior of aqueous suspensions consisting of magnetite particles of two size populations, in the micrometer and nanometer scale, respectively. Previous works on the magnetorheology of oil-based fluids demonstrated that the addition of nanoparticles has a very significant effect on the intensity of the magnetorheological effect. The present contribution confirms such results in the case of aqueous fluids, based on the dependence of the yield stress and the viscosity of the bimodal suspensions on both the composition of the mixtures and the magnetic field strength. It is demonstrated that for a given concentration of micrometer particles, increasing the amount of nanometer magnetite provokes a clear enhancement in the yield stress for all the magnetic fields applied. This is proposed to be due to the formation of heterogeneous aggregates that improve the stability of the suspensions and ease the building of well-arranged field-induced structures. The behavior of both the yield stress and the post-yield viscosity agrees better with the predictions of standard chain models when the relative proportion of both types of particles confers optimum stability to the bimodal dispersions.

Study of the magnetorheological response of aqueous magnetite suspensions stabilized by acrylic acid polymers.

In this paper we describe the magnetorheological (MR) behavior of aqueous suspensions consisting of magnetite particles stabilized by poly(acrylic acid) polymers (PAA). A previous work on the colloidal stability of the same systems for different pH values and polymer concentrations demonstrated that the addition of PAA polymers has a very significant effect on the stability. In the present contribution, we study the MR effect of the suspensions stabilized by two different commercial polymers, as a function of pH, magnetic field strength and magnetite volume fraction. All the results are discussed in terms of the interfacial properties of the systems. It is demonstrated that for a given concentration of micrometer particles, the rheological response strongly depends on pH, on the volume fraction of magnetite particles, on the type of polymer added for increasing the stability and on the magnetic field strength. Changing the polymer used provokes clear rheological differences for the same sample conditions (field strength, volume fraction and pH). This is suggested to be due to the hydrophobic/hydrophilic balance of the polymer affecting the magnetic field ability to form magnetic structures by aggregation of the magnetized particles. The results are compared to the predictions of the so-called standard chain model, based on the assumption that the MR effect is the result of the balance between the magnetic interactions (tending to establish some degree of order in the suspension by formation of particle chains in the direction of the field) and hydrodynamic ones (tending to destroy the formed structures by viscous stress on the chains). It is found that the behavior of the yield stress does not agree well with the predictions of the model when the relative proportion of both particle and polymer confers optimum stability to the dispersions. This is likely due to the fact that the presence of the stabilizing polyelectrolyte provokes that the magnetic field is not as effective in structuring the suspension as deduced from the chain model.

Study of the colloidal stability of concentrated bimodal magnetic fluids.

In this paper, we describe an investigation of the stability and sedimentation behavior of moderately concentrated suspensions of extremely bimodal magnetite particles, including micro- (diameter 1450 nm) and nano- (diameter 8 nm) units. An original method is used, based on the determination of the time dependence of the inductance of a coil surrounding the suspensions. The method proves to be very useful for the determination of the volume fraction of magnetic material in the sensed volume. The observed changes in the resonant frequency of a parallel LC circuit demonstrate that the addition of the magnetite nanoparticles improves the stability and slows down the settling rate of the mixed suspensions. It is proposed that the observed behavior is the result of competition between two processes. One is the formation of a cloud of nanoparticles around the large magnetite units, by virtue of which the latter are maintained at distances beyond the range of DLVO and magnetic attractive interactions. At long times, these composite units will eventually sediment when some critical size is reached, as the small particles are progressively associated with the large ones. The second mechanism is mainly predominant at short times and is related to the higher viscosity of the dispersion medium (the nanoparticles dispersed in the base fluid) for higher nanoparticle concentrations. The stability of the suspensions is discussed in terms of the competition between the two mechanisms.

Stability of mixtures of charged silica, silica-alumina, and magnetite colloids.

We report experiments on the stability of aqueous mixtures of charged colloidal magnetite and charged silica and silica covered with alumina particles of similar size. First, positively charged magnetite dispersions were mixed with negatively charged silica dispersions at pH 4, at different volume ratios and low colloid volume fractions, producing mixtures which were stable over a period of weeks despite the expected electrostatic attraction between the oppositely charged particles. When magnetite particles were mixed with positively charged silica covered with alumina at pH 4 under exactly the same conditions, some of the systems separated to form a magnetite sediment. When the volume fraction of the initial dispersions was increased, the behavior of the mixtures was the opposite: positive magnetite/negative silica mixtures were unstable at intermediate volume ratios. The unexpected behavior of the mixtures was investigated by means of electrophoretic mobility, initial susceptibility, and dynamic light scattering measurements as well as sedimentation experiments.

Stabilization of magnetorheological suspensions by polyacrylic acid polymers.

This work is devoted to the synthesis and stabilization of magnetorheological suspensions constituted by monodisperse micrometer-sized magnetite spheres in aqueous media. The electrical double-layer characteristics of the solid/liquid interface were studied in the absence and presence of adsorbed layers of high molecular weight polyacrylic acids (PAA; Carbopol). Since the Carbopol-covered particles can be thought of as "soft" colloids, Ohshima's theory was used to gain information of the surface potential and the charge density of the polymer layer. The effect of the pH of the solution on the double-layer characteristics is related to the different conformations of the adsorbed molecules provoked by the dissociation of the acrylic groups present in polymer molecules. The stability of the suspensions was experimentally studied for different pH and polymer concentrations, and in the absence or presence of a weak magnetic field applied. The stability of the suspensions was explained using the classical DLVO theory of colloidal stability extended to account for hydration, steric, and magnetic interactions between particles. Diagrams of potential energy vs interparticle distance show the predominant effect of steric, hydrophilic/hydrophobic, and magnetic interactions on the whole stability of the system. The best conditions to obtain stable suspensions were found when strong steric and hydrophilic repulsions hinder the coagulation between polymer-covered particles, simultaneously avoiding sedimentation by the thickening effect of the polymer solution. When a not too high molecular weight PAA was employed in a low concentration, the task of a long-time antisettling effect compatible with the desired magnetic response of the fluid was achieved.

Interfacial and rheological properties of humic acid/hematite suspensions.

This work deals with the effect of humic acid (HA) adsorption on the interfacial properties, the stability, and the rheology of aqueous iron oxide (hematite) suspensions. It is first of all demonstrated that HA effectively adsorbs onto hematite, mainly at acid pH. Since the charge of the HA chains is negative, it will be electrostatically attracted to the hematite surface below the point of zero charge of the particles, when they are positively charged. Electrophoresis measurements of hematite suspensions as a function of pH in the presence and absence of HA clearly demonstrate the adsorption of negatively charged entities on the oxide. Since the HA-covered particles can be thought of as "soft" colloids, Ohshima's theory was used to gain information on the surface potential and the charge density of the HA layer (H. Ohshima, in: A.V. Delgado (Ed.), Interfacial Electrokinetics and Electrophoresis, Dekker, New York, 2002, p. 123). A different procedure was also used to ascertain the degree of modification experienced by the hematite surface when placed in contact with HA solutions. The contact angles of selected liquids on pretreated hematite layers lead to the conclusion that the humic acid molecules impart to the particles a significant electron-donor character, in turn increasing their hydrophilicity. All this amount of information is used in the work for the interpretation of the rheological properties of hematite suspensions; the results are consistent with a stabilizing effect of HA adsorption on the suspensions, mainly as a consequence of the increased electrostatic repulsion between particles.