Incorporation and release of drug into/from superparamagnetic iron oxide nanoparticles

The aim of this study was to attach a model drug (naproxen) onto superparamagnetic iron oxide nanoparticles (SPION). First, SPION were coated with thin layer of silica that contained micropores. We demonstrated that such surface functionalization could be optimized by the use of citric acid which prevented SPION agglomeration during the procedure. HRTEM investigation showed a uniform 1-2-nm-thick silica coating around SPION. This coating did not affect significantly the magnetic properties of the SPION. Into the coated SPION we successfully incorporated about 30 wt% of naproxen. The latter was readily released after immersion into a testing solution. The composites could be interesting for potential use in diagnostics.     

Magnetic nanoparticles for environmental and biomedical applications: A review

Engineered magnetic nanoparticles (MNPs) hold great potential in environmental, biomedical, and clinical applications owing to their many unique properties. This contribution provides an overview of iron oxide MNPs used in environmental, biomedical, and clinical fields. The first part discusses the use of MNPs for environmental purposes, such as contaminant removal, remediation, and water treatment, with a focus on the use of zero-valent iron, magnetite (Fe₃O₄), and maghemite (γ-Fe₂O₃) nanoparticles, either alone or incorporated onto membrane materials. The second part of this review elaborates on the use of MNPs in the biomedical and clinical fields with particular attention to the application of superparamagnetic iron oxide nanoparticles (SPIONs), which have gained research focus recently owing to their many desirable features such as biocompatibility, biodegradability, ease of synthesis and absence of hysteresis. The properties of MNPs and their ability to work at both cellular and molecular levels have allowed their application in vitro and in vivo including drug delivery, hyperthermia treatment, radio-therapeutics, gene delivery, and biotherapeutics. Physiochemical properties such as size, shape, and surface and magnetic properties as well as agglomeration of MNPs and methods to enhance their stability are also discussed.     

Preparation of a biocompatible magnetic film from an aqueous ferrofluid

Very promising nanoparticles for biomedical applications or in medical drug targeting are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. Polyvinyl alcohol (PVA) is a unique synthetic biocompatible polymer that can be chemically cross-linked to form a gel. Biotechnology applications of magnetic gels include biosensors, targeted drug delivery, artificial muscles and magnetic buckles. These gels are produced by incorporating magnetic materials in the polymer composites. In this paper we report the synthesis of an aqueous ferrofluid and the preparation of a biocompatible magnetic gel with polyvinyl alcohol and glutharaldehyde (GTA). HClO₄ was used to induce the peptization since this kind of ferrofluid does not have surfactant. The magnetic gel was dried to generate a biocompatible film.     

Modulation of Relaxivity,Suspension Stability,and Biodistribution of Dendronized Iron Oxide Nanoparticles as a Function of the Organic Shell Design

Nanoparticles (NPs) with a mean diameter of 10 nm are functionalized with three dendrons: D1 a PEGylated PAMAM dendron of generation 0.5, D2 a hydrophilic oligoethyleneglycol‐derivatized dendron (D2) displaying a phosphonic acid at the focal point, and D2–2P the same dendron than D2 but with two phosphonic acid anchoring agents. Their grafting is confirmed by IR spectroscopy and elemental analysis. All dendronized NPs are stable over a long period of time in suspensions in water and in different physiological media and display a mean hydrodynamic diameter smaller than 50 nm whatever the molecule architecture. NMRD profiles and relaxivity measurements highlight the influence of the molecule architecture on the water diffusion close to the magnetic core thus influencing the relaxation properties at low magnetic field. The high hydrophilic architecture of the dendron D2 by contrast to dendron D1 allows maintaining the colloidal stability in different conditions while ensuring a very good accessibility of water molecule close to the magnetic core. Coupling of a fluorescent dye on dendrons have allowed investigating the biodistribution of dendronized NPs, which are found to be quickly eliminated through urinary and hepatobiliary pathways within 4 h. Furthermore, no enhanced permeation and retention effect in tumors can be observed.     

Nanoparticles as an emerging tool to alter the gene expression: Preparation and conjugation methods

Many human diseases occur due to the over or under-expression of genes which can be corrected either by silencing or over-expression, respectively by transforming with specific nucleic acid (NA). NA transformation for medical purposes to alter the cellular gene expression is challenging because NA cannot cross efficiently the cellular biomembrane. One option, the viral vectors, is risky for patients and, the non-viral vectors have lower transformation efficiency. From the past few years, nanoparticles (NPs) are being studied extensively for their use as a vector to deliver NA. They are of a sub-micron size, have a large surface area, rapid absorption ability and can reach inside of the cells. These properties make them a suitable gene carrier. NPs types - organic, inorganic, organic/inorganic hybrid and polymeric NPs, having different properties that can be used to deliver the NA. They possess various properties like biocompatibility, targeted delivery of gene, controlled release of NA which makes them suitable for different uses. In this review, we are describing and comparing various methods to synthesize various kinds of NPs and how they can be conjugated with NA. A series of modifications in NPs to form the polyplex are also discussed along with the varying outcomes in terms of changes in the gene expression and its cytotoxicity towards different cell lines. This review is helpful for nano-scientists to decide which method to be followed for a specific need via controlling gene expression.     

Optimization of sonochemical method of functionalizing Amino-Silane on superparamagnetic iron oxide nanoparticles using Central Composite Design

Optimization of sonochemical method of functionalizing a Silane coupling agent, Amino-Silane on Superparamagnetic Iron Oxide Nanoparticles (SPION) using Central Composite Design is reported. The Amino-Silane is grafted on the SPION in an iced bath environment using a Vibra-Cell 20 kHz ultrasonic irradiator with 13 mm diameter horn. Throughout the experiment amplitude of the ultrasonic device is maintained at 47%. The percentage atomic compositions of various APTES elements which bind to the SPION due to the ultrasonic irradiation were determined using X-ray photoelectron spectrometer (XPS). The influence of ultrasonic irradiation time and amount of APTES required for facile, rapid and effective functionalization of Organo-metallic compound on SPION are optimized. The optimized sonication time and amount of APTES are 8.49 min and 3.40 ml, respectively. The predicted results were validated with experimental data. Using the optimized values APTES were functionalized on the SPION experimentally and the results were compared. The experimental results validate the predicted data. Results show that very minimum sonication time is required for effective grafting of APTES on SPION.     

Synthesis of poly(2-acetamidoacrylic acid) and its PEGMA block copolymer via ATRP in water

Controlled polymerization of a captodative monomer, 2-acetamidoacrylic acid (AAA), was studied for the first time in the literature. Salt of the monomer in water was polymerized using ATRP method and influence of several factors, including solvent composition, halogen exchange and additives like pyridine and halide salts were investigated to improve the control. Captodative monomers form very stable radicals favoring the active species over the dormant one. Depolymerization at room temperature under ATRP conditions was determined as the major obstacle in front of the high molecular weight polymers and block copolymer formation. Nevertheless, poly(AAA-b-(AAA-co-PEGMA)) block polymers were prepared through ATRP and possible applications were discussed. As an example, pH responsive nature and ability to coat superparamagnetic iron oxide nanoparticles were demonstrated.     

Stability of biomimetic ferrofluids established by a systematic study using microwave irradiation at defined wattages

An established biomimetic process for the synthesis of aqueous ferrofluids using polymers has been subjected to systematic microwave irradiation at different wattages primarily to see if the magnetization could be increased by microwave irradiation and if so how would it affect the stability of the fluid. Care has been taken to maintain ambient conditions of synthesis even after three cycles of microwave irradiation before oxidation and ten cycles after it, so as not to violate the basic principles of the process. Detailed characterization using, x-ray diffractometry, transmission electron microscopy, fourier transform infra-red spectroscopy, dynamic light scattering, thermo-gravimetric analysis, differential thermal analysis and vibrating sample magnetometry showed that these fluids containing iron oxide nanoparticles-poly(vinyl) alcohol nanocomposites are highly stable in the proportions established by us. Measurements at five different wattages double the saturation magnetization but the stability remains unaffected compared to the one without microwave irradiation, forcing us to believe that the incubation of the iron salt solution and the polymer in the right proportion before oxidation is what contributes to the stability and that increasing the number of cycles of microwave irradiation at this stage, perhaps, would have led to a more pronounced effect.     

Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F₅-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F₅-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.