ABSTRACT
We report a facile approach for the in situ synthesis of very small iron oxide nanoparticles on the surface of high-quality graphene sheets. Our synthetic strategy involved the direct, liquid-phase exfoliation of highly crystalline graphite (avoiding any oxidation treatment) and the subsequent chemical functionalization of the graphene sheets via the well-established 1,3-dipolar cycloaddition reaction. The resulting graphene derivatives were employed for the immobilization of the nanoparticle precursor (Fe cations) at the introduced organic groups by a modified wet-impregnation method, followed by interaction with acetic acid vapours. The final graphene-iron oxide hybrid material was achieved by heating (calcination) in an inert atmosphere. Characterization by X-ray diffraction, transmission electron and atomic force microscopy, Raman and X-ray photoelectron spectroscopy gave evidence for the formation of rather small (<12 nm), spherical, magnetite-rich nanoparticles which were evenly distributed on the surface of few-layer (<1.2 nm thick) graphene. Due to the presence of the iron oxide nanoparticles, the hybrid material showed a superparamagnetic behaviour at room temperature.
ABSTRACT
PURPOSE: To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG) copolymers for the stabilization of graphene oxide (GO) aqueous dispersions and the feasibility of using the PLA-PEG stabilized GO as a delivery system for the potent anticancer agent paclitaxel. METHODS: A modified Staudenmaier method was applied to synthesize graphene oxide (GO). Diblock PLA-PEG copolymers were synthesized by ring-opening polymerization of dl-lactide in the presence of monomethoxy-poly(ethylene glycol) (mPEG). Probe sonication in the presence of PLA-PEG copolymers was applied in order to reduce the hydrodynamic diameter of GO to the nano-size range according to dynamic light scattering (DLS) and obtain nano-graphene oxide (NGO) composites with PLA-PEG. The composites were characterized by atomic force microscopy (AFM), thermogravimetric analysis (TGA), and DLS. The colloidal stability of the composites was evaluated by recording the size of the composite particles with time and the resistance of composites to aggregation induced by increasing concentrations of NaCl. The composites were loaded with paclitaxel and the in vitro release profile was determined. The cytotoxicity of composites against A549 human lung cancer cells in culture was evaluated by flow cytometry. The uptake of FITC-labeled NGO/PLA-PEG by A549 cells was also estimated with flow cytometry and visualized with fluorescence microscopy. RESULTS: The average hydrodynamic diameter of NGO/PLA-PEG according to DLS ranged between 455 and 534 nm, depending on the molecular weight and proportion of PLA-PEG in the composites. NGO/PLA-PEG exhibited high colloidal stability on storage and in the presence of high concentrations of NaCl (far exceeding physiological concentrations). Paclitaxel was effectively loaded in the composites and released by a highly sustained fashion. Drug release could be regulated by the molecular weight of the PLA-PEG copolymer and its proportion in the composite. The paclitaxel-loaded composites exhibited cytotoxicity against A549 cancer cells which increased with incubation time, in conjunction with the increasing with time uptake of composites by the cancer cells. CONCLUSION: Graphene oxide aqueous dispersions were effectively stabilized by water-dispersible, biocompatible and biodegradable PLA-PEG copolymers. The graphene oxide/PLA-PEG composites exhibited satisfactory paclitaxel loading capacity and sustained in vitro drug release. The paclitaxel-loaded composites could enter the A549 cancer cells and exert cytotoxicity. The results justify further investigation of the suitability of PLA-PEG stabilized graphene oxide for the controlled delivery of paclitaxel.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Drug Carriers , Graphite/chemistry , Oxides/chemistry , Paclitaxel/chemistry , Polyesters/chemistry , Polyethylene Glycols/chemistry , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Chemistry, Pharmaceutical , Colloids , Delayed-Action Preparations , Drug Stability , Feasibility Studies , Flow Cytometry , Humans , Kinetics , Light , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Microscopy, Atomic Force , Microscopy, Fluorescence , Nanoparticles , Paclitaxel/administration & dosage , Paclitaxel/metabolism , Particle Size , Scattering, Radiation , Sodium Chloride/chemistry , Solubility , Sonication , Technology, Pharmaceutical/methods , ThermogravimetryABSTRACT
Fundamental properties such as cation exchange capacity (CEC), permanent charge, pH(PZC), and metal uptake of a Zn-containing montmorillonite are modified, in a predictable manner, by a mild chemical treatment using acetate. Acetate treatment allows a controllable increase of the CEC of montmorillonite up to 180 mequiv/100 g. The CEC of the clay is increasing for decreasing Zn content, with a slope of Delta[Zn]/Delta[CEC] approximately -2. X-ray powder diffraction analysis shows that the lamellar structure of the clay remains unaltered by the acetate treatment, while XPS substantiates the removal of Zn. H(+) uptake data show that the intrinsic protonation pK values and concentration of the variable charge sites ( identical with SOH) are not modified by the acetate treatment. In contrast, the concentration of the permanent charge sites ( identical with X(-)) increased linearly with Zn removal by acetate, leading to a significant H(+) and Cd(2+) uptake enhancement. A physical model is suggested where acetate removes Zn ions strongly bound in the clay, and this in turn modulates the permanent charge and the CEC of the clay.
