Magnetic Nanoemulsions Research Articles

Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone.

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

Magnetic nanoemulsion aided optical defect detection in carbon steel components: Effect of defect width variation on optical contrast

Optical detection of defects of varying widths in ferromagnetic steel components is carried out using polyacrylic acid stabilized magnetic nanoemulsions (MNEs). Magnetic field lines are leaked from the defect regions, due to permeability variation, when a defective ferromagnetic steel component is magnetized. Under the influence of such magnetic flux leakage (MFL), the MNE droplets exhibit orientational ordering, where the inter-droplet separation within the chains varies with the strength of the magnetic field. Exploiting this tunable optical grating phenomenon, wide area naked eye visualization of the surface opening and buried defects is carried out. The defect morphology is accurately estimated using a double thresholding-based image processing technique. The optical contrast varies non-monotonically with defect width for the surface opening defects, which is due to the formation of the surface dipoles on the defect edges. The surface dipoles are strongly coupled for lower defect width due to smaller spatial separation, which causes the MFL to be lower. With increasing defect width, the surface magnetic field lines are diffused leading to a lowering of the MFL. In between, for ∼2 mm wide defect, MFL is the highest and the generated optical contrast is found to be the strongest. The MFL profiles are numerically estimated using finite element modeling and experimentally verified using a Hall probe. The cross correlation between the generated optical contrast and MFL magnitudes clearly demonstrates the non-monotonic effect of defect width on the optical contrast of the MNE-based sensors for large area naked eye non-destructive defect detection in ferromagnetic materials.

Probing concentration and time dependent conformational changes in poly acrylic acid stabilized magnetic nanoemulsion using magnetic chaining-based inter-droplet force measurement

Emulsions are stabilized with surfactants, polymers, or polyelectrolytes to extend their shelf-life and colloidal stability. Electro-steric interaction in polyelectrolyte stabilized emulsions makes them ideal systems for probing the conformational dynamics. Here, magnetic chaining technique is exploited for inter-droplet force measurement in poly acrylic acid (PAA) stabilized magnetic nanoemulsions, and to probe the conformational changes of the stabilizing moieties as a function of time and PAA concentration. Force measurement studies indicate an increased inter-droplet spacing for higher concentration of PAA due to an increase in osmotic pressure with concentration. Further, for a fixed concentration, the inter-droplet spacing decreases with time due to the slow diffusion of the polymer chains resulting in conformational changes. This is the first experimental report on conformational dynamics of PAA stabilized oil-in-water magnetic nanoemulsions. The obtained results are beneficial for understanding the nature of colloidal interaction forces in polyelectrolyte stabilized nanoemulsions.

Approaches on Ferrofluid Synthesis and Applications: Current Status and Future Perspectives.

Ferrofluids are colloidal suspensions of iron oxide nanoparticles (IONPs) within aqueous or nonaqueous liquids that exhibit strong magnetic properties. These magnetic properties allow ferrofluids to be manipulated and controlled when exposed to magnetic fields. This review aims to provide the current scope and research opportunities regarding the methods of synthesis of nanoparticles, surfactants, and carrier liquids for ferrofluid production, along with the rheology and applications of ferrofluids within the fields of medicine, water treatment, and mechanical engineering. A ferrofluid is composed of IONPs, a surfactant that coats the magnetic IONPs to prevent agglomeration, and a carrier liquid that suspends the IONPs. Coprecipitation and thermal decomposition are the main methods used for the synthesis of IONPs. Despite the fact that thermal decomposition provides precise control on the nanoparticle size, coprecipitation is the most used method, even when the oxidation of iron can occur. This oxidation alters the ratio of maghemite/magnetite, influencing the magnetic properties of ferrofluids. Strategies to overcome iron oxidation have been proposed, such as the use of an inert atmosphere, adjusting the Fe(II) and Fe(III) ratio to 1:2, and the exploration of other metals with the oxidation state +2. Surfactants and carrier liquids are chosen according to the ferrofluid application to ensure stability. Hence, a compatible carrier liquid (polar or nonpolar) is selected, and then, a surfactant, mainly a polymer, is embedded in the IONPs, providing a steric barrier. Due to the variety of surfactants and carrier liquids, the rheological properties of ferrofluids are an important response variable evaluated when synthesizing ferrofluids. There are many reported applications of ferrofluids, including biosensing, medical imaging, medicinal therapy, magnetic nanoemulsions, and magnetic impedance. Other applications include water treatment, energy harvesting and transfer, and vibration control. To progress from synthesis to applications, research is still ongoing to ensure control of the ferrofluids’ properties.

Manganese Ferrite Nanoparticles Encapsulated into Vitamin E/Sphingomyelin Nanoemulsions as Contrast Agents for High-Sensitive Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is one of the most powerful non-invasive imaging modalities used in clinics due to its great spatial resolution and excellent soft-tissue contrast, though still less sensitive than other techniques such as the nuclear imaging modalities. This lack of sensitivity can be improved with the use of contrast agents based on nanomaterials. In recent years, researchers have focused on the development of magnetic nanoparticles, given their role as enhancers of the contrast signal based on the magnetic resonance. Manganese ferrite nanoparticles stand out, given their high magnetic susceptibility and magnetic soft nature. Herein, 10nm MnFe2 O4 nanoparticles, functionalized with the natural antioxidant vitamin E (VitE-MFO) are encapsulated into simple, biodegradable and non-toxic nanoemulsions (NEs), by a reproducible one-step method obtaining stable 150nm-sized magnetic nanoemulsions (VitE-MFO-NEs). After encapsulation, the superparamagnetic properties of VitE-MFO are maintained and MR imaging studies reveal an extremely high transverse relaxivity for VitE-MFO-NEs (652.9×10-3 m-1 s-1 ), twofold higher than VitE-MFO value. Moreover, VitE-MFO-NEs show great in vivo biocompatibility and good signal in in vivo and ex vivo MRI, which indicates their great potential for biomedical imaging enhancing the negative MR contrast and significantly improving the sensitivity of MRI.

Poly acrylic acid stabilized magnetic nanoemulsions for visual defect detection: Effect of pH on detection sensitivity and colloidal stability

Magnetic field assisted tunable colour contrast in magnetic nanoemulsions is exploited for visual detection of defects in ferromagnetic components. We demonstrate an enhanced defect detection sensitivity by stabilizing oil-in-water magnetic nanoemulsion with poly acrylic acid (PAA) at varying pH. In this detection technique, the variation of magnetic permeability, in the vicinity of the defects, causes magnetic flux leakage, which results in a distinct colour contrast on the magnetic nanoemulsion sensor due to the formation of anisotropic periodic structures, parallel to the external field direction, where the inter-droplet spacing within the linear chains depends on the effective magnetic flux. By exploiting this colour and magnetic flux dependence, severity of the defects is assessed by observing the colour contrast. Our studies indicate that defect detection sensitivity decreases with increasing pH due to globule-to-coil conformational transition of the interfacial PAA molecules. With increasing pH, the PAA network swells due to mobile counter-ions induced osmotic pressure and electrostatic repulsion between the charged monomer units, leading to a solvated coil-like configuration, which is confirmed from the increase in hydrodynamic diameter and zeta potential. The inter-droplet force measurements show an increase in decay length by ~3.5 times, when pH is increased from ~1.5 to ~4.0. The lower decay length at pH ~ 1.5 indicates the formation of linear chain-like structures with smaller inter-droplet spacing near the defect edges, where the magnetic flux leakage is maximum. This results in a fewer number of randomly oriented droplets at the defect centre, thereby enhancing the defect detection sensitivity at lower pH. However, nanoemulsions stabilized at pH > 3 show increased colloidal stability, as compared to pH ~ 1.5. Our studies indicate that nanoemulsions at pH ~ 3.5 exhibit an optimum colloidal stability with good defect detection sensitivity. The obtained results are beneficial for developing high sensitivity, reliable and reusable magnetic nanoemulsion sensors for naked eye visualization of defects in ferromagnetic components.

Magnetic nanoemulsions as candidates for Alzheimer’s disease dual imaging theranostics

Alzheimer’s disease (AD) is the most prevalent cause of dementia linked to the accumulation of amyloid-beta (Aβ) plaques-fibrils that impair cognitive functions. Magnetic nanoparticles (MNPs) are emerging as promising tools for the crusade against AD owning to appropriate biocompatibility and facile functionalization that can lead to theranostic agents. Herein, the fabrication of a multimodal (magnetic resonance imaging (MRI), fluorescence imaging, and drug carrier) magnetic nanoemulsion (MNE) is reported as an AD theranostic candidate. Initially zinc ferrite MNPs of high saturation magnetization (129 emu g−1) were synthesized through a modified microwave-assisted polyol process. Memantine (a registered AD drug) was labeled with fluorescein (Mem-Flu) and encapsulated with the MNPs in sodium dodecyl sulfate micelles to form the MNE. Small hydrodynamic size (107), high encapsulation (77.5%) and loading efficiencies (86.1%) and sufficient transverse relaxivity (48.7 mM−1 s−1) were achieved through the design while sustained release of Mem-Flu was unveiled by in zero-order, first-order, Higuchi and Korsmeyer–Peppas pharmacokinetic models. Moreover, the MNE acquired fluorescence imaging ability of Aβ1–42 peptide monomers and/or plaques-fibrils via the fluorescein labeling of Memantine. A novel inorganic-organic hybrid multimodal AD theranostic candidate is presented.

Visual detection of defects in carbon steel using magnetic nanoemulsions: Effect of stabilizing moieties on the defect detection sensitivity

The defect detection sensitivity of magnetic nanoemulsions (MNEs) stabilized with different functional moieties such as anionic surfactant, co-polymer and a weak polyelectrolyte is reported here. The visually discernible colour contrast over the defective regions and the corresponding Bragg’s reflection, originating from the linear chain-like structures formed by the leakage magnetic flux are experimentally measured and compared with the theoretically obtained profiles. The linear chain-like structures, formed by the MNEs, are also visualized using atomic force and optical phase contrast microscopy studies. Defect detection studies are carried out on carbon steel samples with artificially made defects (rectangular slots) and the variations in defect detection sensitivity (colour contrast) are assessed under different stabilizing moieties. It is found that the electrostatically stabilized MNEs exhibited superior defect detection sensitivity, as compared to the polymeric stabilizers. The microscopic origin for sensitivity variations, is studied by measuring the inter-droplet forces and hydrodynamic diameter. The inter-droplet force measurements show that the lower decay length is better for improving the defect detection sensitivity. Through image processing and intensity profiling, the defect widths are accurately estimated, which are in good agreements with the actual defect dimensions. The intensity profiles are found to vary linearly with the defect depth for the shallower defects. These results are useful to tailor MNEs with superior defect detection sensitivity and long-term stability towards development of MNE-based thin film sensors for automated and superior defect detection strategies.

Enhanced magnetic heating efficiency at acidic pH for magnetic nanoemulsions stabilized with a weak polyelectrolyte

HypothesisMagnetic fluid hyperthermia has attracted considerable attention for cancer therapeutics. Magnetic nanoemulsions are potential candidates for multi-modal hyperthermia due to the possibility of volumetric loading with suitable chemo/photo-therapy agents. Often, the nanocarriers are stabilized using organic molecules that behave differently under varying pH and hence, an understanding of their interfacial behaviour is important for practical applications. ExperimentsWe probe the magnetic heating efficiency of poly acrylic acid (PAA) stabilized oil-in-water magnetic nanoemulsions, as a function of pH, where the conformational changes of the PAA molecules are studied using dynamic light scattering and inter-droplet force measurements. FindingsA ~50% enhanced heating efficiency is observed when solution pH is reduced from ~9 to 3, which is attributed to the coil-to-globule conformational changes of the PAA molecules. The increased ionization of the carboxylic acid groups, at higher pH, leads to reduced hydrophobicity that results in an increase in the interfacial thermal resistance causing a lower magneto-thermal heating efficiency at higher pH. The proposed interfacial heat transfer hypothesis is experimentally verified using thermal imaging, where a lower rate of heat transfer is obtained at higher pH. The observed enhanced hyperthermia efficiency at low pH is beneficial for designing efficient pH-responsive nano-carriers for multi-modal hyperthermia.

Effect of orientational ordering of magnetic nanoemulsions immobilized in agar gel on magnetic hyperthermia

Magnetic nanoemulsions of droplet size ∼200 nm, loaded with single domain superparamagnetic nanoparticles (MNP), are potential candidates for multimodal hyperthermia due to availability of large loading volume and enhanced permeation and retention (EPR) in the cancerous tissues. In such nanoemulsions, radio frequency alternating magnetic field induced heating occur at two entirely different length scales, viz. Neel-Brown relaxation of the dispersed MNP and Brownian relaxation of emulsion droplets. Here we study the effects of orientation ordering or texturing of droplets, immobilized in a tissue mimicking agar matrix, on the field induced heating efficiency. A higher specific absorption rate (maximum ∼73 ± 2 W/gFe) is observed for droplets orientated parallel to the direction of the alternating magnetic field because of the enhancement of effective uniaxial anisotropy energy density and increased effective relaxation time. For identical and non-interacting MNP oriented parallel to the external DC magnetic field, a threefold increase in the effective uniaxial anisotropy energy density and ∼20–30% increased specific absorption rate are observed as compared to those oriented perpendicular to the magnetic field. Magnetic force microscopy images showed that the spherical morphology of the droplets remains intact even after orientational ordering and average topographic height of the droplets are found to be ∼220 (±17) nm, which is in good agreement with the most probable size obtained from dynamic light scattering. The residual volume magnetization of the emulsion droplets is found to be 1.1 × 10−6 emu/cc, indicating the superparamagnetic nature of the droplets in tissue equivalent environment. The observed increase in heating efficiency of the immobilized and oriented emulsion droplets shows promising applications in multimodal hyperthermia therapy because of the requirement of lower dose of MNP and shorter treatment time.

Preparation of Robust Metal-Free Magnetic Nanoemulsions Encapsulating Low-Molecular-Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery.

With a view to developing a theranostic nanomedicine for targeted drug delivery systems visible by magnetic resonance (MR) imaging, robust metal-free magnetic nanoemulsions (mean particle size less than 20 nm) consisting of a biocompatible surfactant and hydrophobic, low molecular weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals were prepared in pH 7.4 phosphate-buffered saline (PBS). The structure of the nanoemulsions was characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small-angle neutron-scattering measurements. The nanoemulsions showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T1 ) weighted MR images in PBS in vitro (and preliminarily in vivo). Furthermore, the hydrophobic anticancer drug paclitaxel could be encapsulated inside the nanoparticles, and the resulting paclitaxel-loaded nanoemulsions were efficiently incorporated into HeLa cells to suppress cell growth.

Magnetic Nanoemulsions: Comparison between Nanoemulsions Formed by Ultrasonication and by Spontaneous Emulsification.

Nanoemulsions are particularly suitable as a platform in the development of delivery systems. The type of nanoemulsion with a higher stability will offer an advantage in the preparation of a delivery system for lipophilic drugs. Nanoemulsions can be fabricated by different processing methods, which are usually categorized as either high- or low-energy methods. In this study, a comparison between two methods of preparing magnetic oil-in-water (O/W) nanoemulsions is described. The nanoemulsions were formed by sonication (the high-energy method) or by spontaneous emulsification (the low-energy method). In both cases, the oil phase was olive oil, and a phospholipid and a pegylated phospholipid were used as emulsifiers. To favor the comparison, the amounts of the components were the same in both kinds of nanoemulsions. Moreover, nanoemulsions were loaded with hydrophobic superparamagnetic nanoparticles and indomethacin. In vitro, releases studies indicated a short drug burst period followed by a prolonged phase of dissolutive drug release. The Korsmeyer-Peppas model can fit the associated kinetics. The results showed that such nanoemulsions are suitable as a platform in the development of delivering systems for lipophilic drugs. The long-term stability was also examined at different temperatures, as well as the interaction with plasma proteins. Nanoemulsion obtained by the low-energy method showed a great stability at 4 °C and at ambient temperature. Its size and polydispersity did not change over more than two months. The spontaneous emulsification method therefore has great potential for forming nanoemulsion-based delivery systems.

Magnetic hyperthermia in magnetic nanoemulsions: Effects of polydispersity, particle concentration and medium viscosity

Magnetic fluid hyperthermia (MFH) is a promising cancer treatment modality where alternating magnetic field is used for heating cancerous cells loaded with magnetic nanofluids. Of late, it is realized that magnetic nano-carriers in the size range ∼100–200nm (e.g. magnetic nanocomposites, magnetic liposomes and magnetic nanoemulsions) are ideal candidates for multimodal MFH coupled with drug delivery or photodynamic therapy due to enhanced permeation and retention (EPR) in the leaky vasculature of cancerous tissues. Here, we study the radiofrequency alternating magnetic field induced heating in magnetically polarizable oil-in-water nanoemulsions of hydrodynamic diameter ∼200nm, containing single domain superparamagnetic nanoparticles of average diameter ∼10nm in the oil phase. We probe the effects of size polydispersity of the droplets and medium viscosity on the field induced heating efficiency. The contribution of Neel and Brown relaxation of the magnetic nanoparticles on specific absorption rate (SAR) of the magnetic nanoemulsions, was found to increase linearly with the square of the applied field, with a maximum value of 164.4±4.3W/gFe. In magnetic nanoemulsions, the heating is induced by the Neel-Brown relaxation of the MNP over a length scale of 10nm, and the whole scale Brownian relaxation of the emulsion droplets has over a length scale of 200nm. The magnetic nanoemulsion sample with lower polydispersity (σ=0.2) exhibited a significantly higher SAR value (3.3 times higher) as compared to the sample with larger polydispersity (σ=0.4). The SAR values of the samples with 4.6 and 1.7 wt.% of MNP loading with σ values 0.4 a 0.3, respectively were comparable, suggesting a higher heating efficiency in nanofluid containing particles of lower size polydispersity even at lower particle loading. The emulsion droplets, immobilized in an agar matrix (4wt.%), gave a maximum SAR value of 41.7±2.4W/gFe as compared to 111.8±3.4W/gFe in the case of droplets dispersed in water, which indicate a ∼40–50% drop in SAR due to abrogation of whole scale Brownian relaxation of the emulsion droplets. This suggests the need for improving the heating efficiency during actual therapy in tissues. The residual SAR of the immobilized sample correlates well with the SAR of the magnetic nanofluid, albeit under a lower external field amplitude due to demagnetization effect of the clusters of MNP loaded inside the droplets. The observed heating efficiency of larger sized magnetic nanoemulsion offer new possibilities for multimodal therapy due to availability of large volume for loading anti-cancer drug or photodynamic agents.

Non-enzymatic glucose detection using magnetic nanoemulsions

We probe the optical properties and intermolecular interactions in magnetically responsive nanoemulsions in the presence of glucose. The equilibrium interdroplet distance between the emulsion droplets in an one-dimensional array increases by several nanometers in the presence of glucose because of intermolecular hydrogen bonding with sodium dodecyl sulphate molecules at the oil-water interface that gives rise to stretched lamellae-like structure. The observed large red shift in the diffracted Bragg peak (∼50–100 nm) and the linear response in the glucose concentration range of 0.25–25 mM offer a simple, fast, and cost effective non-enzymatic approach for glucose detection.

A methanol sensor based on stimulus-responsive magnetic nanoemulsions

We demonstrate the methanol detection ability of stimulus-responsive magnetically polarizable nanoemulsions. The oil-in-water type of nanoemulsions of droplet radius ∼100nm is produced by emulsification of Fe3O4 based magnetic nanofluid in presence of water, oil and an anionic surfactant. The nano-emulsion droplets in a cylindrical vial or cuvette placed inside a small solenoid that produces a magnetic field of ∼100Gauss constitute the sensor assembly. It is observed that the presence of methanol in ppm level produces strong changes in the repulsive forces between the nanoemulsion droplets, giving rise to a red shift in the incident white light and a visually perceptible color change of the nanoemulsion. The origin of the red shift is studied by measuring the subtle changes in the intermolecular forces between the emulsion droplets in presence of methanol molecules. We observe that the diffusion of methanol molecules significantly alters the onset of electrostatic repulsion between nanodroplets. The sensor showed a linear detection range of 0–2250ppm and a response time of ∼1s. The present approach is a simple, inexpensive and useful for sensitive detection of methanol in aqueous solution.

Magnetic nanoemulsions as drug delivery system for Foscan ®: Skin permeation and retention in vitro assays for topical application in photodynamic therapy (PDT) of skin cancer

In this work, we performed the synthesis and in vitro characterization of a new class of drug delivery system (DDS) denominated magnetic nanoemulsion (MNE). The association of colloidal nanoparticles with biocompatible magnetic fluids results in a new DDS for application in photodynamic therapy (PDT) and magnetic hyperthermia treatment. It works in a synergic manner with an expected enhancement in tumor damage after minimum drug doses, based on heat dissipation and/or light photosensitization. For this purpose, we investigated the permeation and retention in vitro model using Foscan ® as a photosensitizer incorporated in MNE using a Franz diffusion cell and a biological skin model in biomimetic conditions.

Amino-containing magnetic nanoemulsions: elaboration and nucleic acid extraction

Amino-containing magnetic colloids were prepared from highly magnetic oil-in-water (O/W) emulsions. The functionalization was performed by controlling the adsorption of polyethyleneimine onto negatively charged magnetic emulsions. The cationic magnetic nanodroplets were characterized in terms of chemical composition, particle size, size distribution, zeta potential and colloidal stability as a function of storage time. These amino-containing magnetic emulsions were assessed as a new tool for nucleic acid extraction and amplification. The adsorption of nucleic acids was mostly controlled by attractive electrostatic interactions. The adsorption efficiency of a model RNA was found to be encouraging and the captured nucleic acid molecules were directly enzymatically amplified in the presence of the magnetic particles without any elution step.