Enhancement of the efficiency of magnetic targeting for drug delivery: Development and evaluation of magnet system

Deep magnetic capture and clinical application are the current trends for magnetic targeted drug delivery system. More promising and possible strategies are needed to overcome the current limitations and further improve the magnetic targeting technique. Recent advances in the development of targeting magnet system show promise in progressing this technology from the laboratory to the clinic. Starting from well-known basic concepts, current limitations of magnetic targeted drug delivery system are analyzed. Meanwhile, the design concepts and evaluations of some effective improvements in magnet system are discussed and reviewed with reference to (i) reasonable design of magnet system; (ii) control modes of magnet system used to generate dynamical magnetic fields; and (iii) magnetic field driving types.     

Self-assembled magnetic lamellar hydroxyapatite as an efficient nano-vector for gene delivery

Magnetic lamellar hydroxyapatite (ML-HA) nanoparticles were synthesized by a template-assisted self-assembly process. The as-prepared ML-HA nanoparticles self-assembled under different conditions were characterized by XRD, TEM, cytotoxicity assessment, and DNA-loading and transfection efficiency measurements. We found that the structure and morphology of ML-HA were controlled by self-assembly conditions. The ML-HA synthesized in this work exhibited good biocompatibility. The DNA-loading capacity and ζ-potential of ML-HA were much lower in comparison to bare lamellar HA (L-HA) without magnetic nanoparticles. Despite that, the ML-HA with good lamellar structure showed 47% higher transfection efficiency than L-HA. Results suggested that the ordered lamellar structure is a key factor in controlling transfection efficiency and magnetization is an effective way of improving the transfection efficiency of lamellar HA. Mechanisms were proposed to interpret these experimental results. It is demonstrated that the ML-HA may be a promising gene vector to deliver DNA into the cells effectively and safely.     

Development of magnetically targeted drug delivery system using superconducting magnet

Development of a novel drug delivery system was made to accumulate/navigate magnetic drugs with the help of a superconducting magnet in order to control the drugs in blood vessels located deep inside the body. In the present paper, we tested the feasibility of a novel navigation system, made by applying a strong external (magnetic) field through SmBaCuO and YBaCuO bulk superconductors in order to realize the practice of using externally applied magnetic fields for targeting the magnetic particles to a circumscribed body region.     

Instant magnetic labeling of tumor cells by ultrasound in vitro

Magnetic labeling of living cells creates opportunities for numerous biomedical applications. Here we describe an instantly cell magnetic labeling method based on ultrasound. We present a detailed study on the ultrasound performance of a simple and efficient labeling protocol for H-22 cells in vitro. High frequency focus ultrasound was investigated as an alternative method to achieve instant cell labeling with the magnetic particles without the need for adjunct agents or initiating cell cultures. Mean diameter of 168 nm dextran-T40 coated superparamagnetic iron oxide (SPIO) nanoparticles were prepared by means of classical coprecipitation in solution in our laboratory. H-22 tumor cells suspended in phosphate-buffered saline (PBS, pH=7.2) were exposed to ultrasound at 1.37 MHz for up to 120 s in the presence of SPIOs. The cellular uptake of iron oxide nanoparticles was detected by prussion blue staining. The viability of cells was determined by a trypan blue exclusion test. At 2 W power and 60 s ultrasound exposure in presence of 410 μg/ml SPIOs, H-22 cell labeling efficiency reached 69.4±6.3% and the labeled cells exhibited an iron content of 10.38±2.43 pg per cell. Furthermore, 95.2±3.2% cells remained viable. The results indicated that the ultrasound protocol could be potentially applied to label cells with large-sized magnetic particles. We also calculated the shear stress at the 2 W power and 1.37 MHz used in experiments. The results showed that the shear stress threshold for ultrasonically induced H-22 cell reparable sonoporation was 697 Pa. These findings provide a quantitative guidance in designing ultrasound protocols for cell labeling.     

Numerical study of magnetic nanoparticles concentration in biofluid (blood) under influence of high gradient magnetic field

Ferrofluids are widely used in pharmaceutical industries as magnetic separation tools, anti-cancer drug carriers and micro-valve applications. The purpose of the current study is to investigate the effect of a magnetic field on the volume concentration of magnetic nanoparticles of a non-Newtonian biofluid (blood) as a drug carrier. The effect of particles on the flow field is considered. The governing non-linear differential equations, concentration and Naviar-stokes are coupled with the magnetic field. To solve these equations, a finite volume based code is developed and utilized. The results show accumulation of magnetic nanoparticles near the magnetic source until it looks like a solid object. The accumulation of nanoparticles is due to the magnetic force that overcomes the fluid drag force. As the magnetic strength and size of the magnetic particles increase, the accumulation of nanoparticles increases, as well. The magnetic susceptibility of particles also affects the flow field and the contour of the concentration considerably.     

Formation and properties of magnetic chains for 100 nm nanoparticles used in separations of molecules and cells

Optical observations of 100 nm metallic magnetic nanoparticles are used to study their magnetic field induced self assembly. Chains with lengths of tens of microns are observed to form within minutes at nanoparticle concentrations 10¹⁰/mL. Chain rotation and magnetophoresis are readily observed, and SEM reveals that long chains are not simple single particle filaments. Similar chains are detected for several 100 nm commercial bio-separation nanoparticles. We demonstrate the staged magnetic condensation of different types of nanoparticles into composite structures and show that magnetic chains bind to immuno-magnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations.     

Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI

In vivo visualization of transplanted stem cells with noninvasive technique is essential for the monitoring of cell implantation, homing and differentiation. At present, superparamagnetic iron oxide (SPIO) is most commonly used for cell labeling. However, stem cells lack phagocytic capacity and transfection agent is required for sufficient internalization of SPIO for cellular imaging. However, the potential hazards of transfection agents are not fully investigated. Instead of SPIO, we used commercially available new tagging material, fluorescent magnetic nanoparticle (MNP) containing rhodamine B isothiocyanate within a silica shell (Biterials, Seoul, Korea). This tagging material does not require transfection agents for the cell labeling. In addition to that, the core of this MNP is composed of ferrite and the inner portion of silica shell contains fluorescent materials, therefore, it has both magnetic and optical features. This study was designed to track intrasplenically injected bone marrow mesenchymal stem cells (MSCs) labeled with fluorescent MNP in liver cirrhosis rat model with 3-T magnetic resonance equipment. We compared magnetic resonance imaging (MRI) of livers in rats which were injected with non-labeled stem cells or labeled stem cells with MNP or SPIO. We found that the respective liver-to-muscle contrast-to-noise ratios at 3 and 5 h after MNP or SPIO-labeled stem cell injection was significantly lower than that of pre-injection and non-labeled group. There was no significant difference between MNP-labeled group and SPIO-labeled group. We can effectively detect intrasplenically injected MNP-labeled MSCs in an experimental rat model of liver cirrhosis with 3-T MRI.     

Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells

Accurate delivery of cells to target organs is critical for success of cell-based therapies with stem cells or immune cells such as antigen-presenting dendritic cells (DC). Labeling with contrast agents before implantation provides a powerful means for monitoring cellular migration using magnetic resonance imaging (MRI). In this study, we investigated the uptake of fully synthesized or bacterial magnetic nanoparticles (MNPs) into hematopoietic Flt3⁺ stem cells and DC from mouse bone marrow. We show that (i) uptake of both synthetic and biogenic nanoparticles into cells endow magnetic activity and (ii) low numbers of MNP-loaded cells are readily detected by MRI.     

Application of computed tomography images in the evaluation of magnetic nanoparticles biodistribution

In this work we evaluate the effectiveness of computed tomography images as a tool to determine magnetic nanoparticle biodistribution over biological tissues. For this purpose, tomography images for magnetic nanoparticles, composed of Fe₃O₄, coated with 2,3-dimercaptosuccinic acid (DMSA), were generated at several material concentrations. The comparison of CT numbers, calculated from these images generated at clinical conditions, with typical CT numbers for biological tissues, shows that the detection of nanoparticle in most tissues is only possible for high material concentrations.     

Effect of non-Newtonian characteristics of blood on magnetic targeting in the impermeable micro-vessel

In this investigation we consider to extended the work of Furlani and Furlani [15] by taking non-Newtonian fluid model for the blood in the impermeable micro-vessel. The behavior of blood is considered as the Herschel-Bulkley fluid which is more suitable for the micro-vessel of radius 50 μm. The expression for the fluidic force for the carrier particle traversing in the Herschel-Bulkley fluid is obtained first. Several factors that influence the magnetic targeting of the carrier particles in the microvasculature, such as the size of the carrier particle, the volume fraction of embedded magnetic nanoparticles, and the diameter of the micro-vessel are considered in the present problem. An algorithm is given to solve the system of coupled equations for trajectories of the carrier particle in the invasive case. The trajectories of the carrier particles are found in both invasive and noninvasive targeting systems. A comparison is make regarding the trajectories in these cases. Also, a prediction of the capture of therapeutic magnetic nanoparticle in the human microvasculature is made for different radii and volume fractions in both the invasive and noninvasive cases.     

Application of magnetic nanoparticles in full-automated chemiluminescent enzyme immunoassay

The magnetic nanoparticles (MNPs) Therma-Max™ were used as a carrier to develop an automated sandwich chemiluminescent enzyme immunoassay (CLEIA) to detect thyroid-stimulating hormone (TSH) in a sensitive and specific way. The Therma-Max™ particles allow for automation because, unlike magnetic microspheres, they are completely dispersed in aqueous solution and allow for accurate automatic handling. Signal intensities detected with MNPs were 8-fold higher than those found with conventional micron-sized magnetic particles. A reproducibility study suggests that these particles allow for a stable detection method, as the coefficient of variation (CV) is less than 6% (n=10).     

Application of TiO2 with different structures in solar cells

The application of TiO2-based devices is mainly dependent on their crystalline structure,morphology,size,and exposed facets.Two kinds of TiO2 with different structures,namely TiO2 pompons and TiO2 nanotubes,have been prepared by the hydrothermal method.TiO2 with different structures is characterized by scanning electron microscopy(SEM),X-ray diffraction(XRD),and Brunauer-Emmett-Teller(BET) surface area analysis.Solar cells based on poly(3-hexylthiophene)(P3HT) and TiO2 with different structures are fabricated.In the device ITO/TiO2/P3HT/Au,the P3HT is designed to act as the electron donor,and TiO2 pompons and TiO2 nanotubes act as the electron acceptor.The effects of the TiO2 structure on the performance of hybrid heterojunction solar cells are investigated.The device with TiO2 pompons has an open circuit voltage(Voc) of 0.51 V,a short circuit current(Jsc) of 0.21 mA/cm2,and a fill factor(FF) of 28.3%.Another device with TiO2 nanotubes has a V oc of 0.5 V,J sc of 0.27mA/cm2,and FF of 28.4%.The results indicate that the TiO2 nanotubes with a unidimensional structure have better carrier transport and light absorption properties than TiO 2 pompons.Consequently,the solar cell based on TiO2 nanotubes has a better performance.     

Application of magnetic poly(styrene-glycidyl methacrylate) microspheres for immunomagnetic separation of bone marrow cells

Surface-functionalized magnetic poly(styrene-glycidyl methacrylate) (PS-GMA) microspheres were prepared and coupled with Sca-1 antibody for cell selection from murine bone marrow mononuclear cells (MNCs). Biotinylated Sca-1 antibody could be directly coupled to avidin-bound magnetic microspheres. Alternatively, oxidized goat anti-mouse antibody was covalently bound onto the amino group-containing magnetic microspheres in a site-directed manner, and the resultant conjugate was coupled with non-modified Sca-1 antibody. Using the indirect antibody-bound magnetic microspheres, the purity of isolated Sca-1⁺ cells increased with bead-to-cell ratio. Using a bead-to-cell ratio of 10 beads/cell, a purity of 85% Sca-1⁺ cells corresponding to a 17-fold enrichment was achieved.     

Comparative study on the effect of annealing treatments on RTL mechanism in natural quartz from different origins

The behaviour of trap centres and luminescence centres has been investigated for fired and unfired natural quartz from bricks and sediments irradiated at 100 Gy and annealed at different temperatures in the range 350-700 °C. The annealing treatment affects thermoluminescence (TL) glow curve as various changes were observed. The higher sensitization occurred for an annealing in the region 550-600 °C. At this annealing temperature, it has been observed the emergence of two peaks arising at 96 and 180 °C. At lower annealing temperatures, these peaks are overlapped by the peaks localized at 90 and 195 °C, respectively. Concerning the fired quartz, the higher sensitization occurred for an annealing in the region 500-550 °C for peak temperature around 200 °C and an unusual desensitization for the peak temperature around 100 °C. The behaviour of the two types of quartz is analyzed regarding to their kinetic parameters and luminescence emission and compared to literature data.     

Analysis of feasibility of in vitro nuclear magnetic resonance tracking human umbilical cord mesenchymal stem cells by Gd-DTPA labeled

Objective

Three different kinds of transfection reagents were used to mediate the transfection of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) into human umbilical-cord-derived mesenchymal stem cells (hUCMSCs). The efficacy of different transfection reagents and the feasibility of NMR tracer in vitro of magnetized stem cells were estimated.

Methods

After purification by tissue explants adherent method, the biological characteristics of hUCMSCs in vitro were identified by subculture and amplification. Calcium phosphate, Effectene and liposome2000 were used to transfect Gd-DTPA-labeled hUCMSCs respectively, and cell counting was used to mediate the transfection of Gd-DTPA into hUCMSCs, which were then induced to lipoblast and osteoblast in vitro. The determination of the transfection activities of the transfection reagents was conducted by measuring the magnetic resonance imaging (MRI) signal intensity of the Gd-DTPA-labeled cells and the concentration of gadolinium ion in the cells. Furthermore, the relationship between the signal intensity of Gd-DTPA-labeled hUCMSCsMRI, cell subculture and generations was studied.

Results

Primary cells were obtained by tissue explants adherent for two weeks. The cells displayed a long spindle form and grew in swirl. After two passage generations, the cellular morphology became more homogeneous. The result detected by the flow cytometer showed that CD29C, D44, CD90, and CD105 were highly expressed, while no CD45, CD40, and HLA-DR expression was detected in the third generation cells. Directional induction in vitro caused the differentiation into lipoblast and osteoblast. After transfected by calcium phosphate, Effectene and liposome 2000, the signal intensity of stem cells was 2281.2 ± 118.8, 2031.9 ± 59.7 and 1887.4 ± 40.8 measured by MRI. Differences between these three groups were statistically significant (P < 0.05). The concentrations of gadolinium ion in three groups of stem cells were 0.178 ± 0.009 mg/L, 0.158 ± 0.003 mg/L and 0.120 ± 0.002 mg/L respectively, examined by inductively coupled plasma atomic emission spectrometry. No significant differences were found among these three groups (P < 0.05). The proliferation and differentiation abilities of the Gd-DTPA-labeled stem cells were not affected. A minimum 5 × 10⁴ Gd-DTPA-labeled stem cells could be traced with MRI in vitro and presented in high signal. The trace duration time in vitro was about 12 days.

Conclusions

Tissue explants adherent method can be availably applied to purify hUCMSCs. The Effectene method was proved to have the best transfection effect. The proliferation ability and differentiation potency of Gd-DTPA-labeled hUCMSCs were not affected, and the NMR of labeled stem cells in vitro was proved to be feasible.     

The influence of heat transfer and magnetic field on peristaltic transport of a Newtonian fluid in a vertical annulus: Application of an endoscope

This Letter discusses the influence of heat transfer and magnetic field on the peristaltic flow of Newtonian fluid in a vertical annulus under a zero Reynolds number and long wavelength approximation. The inner tube is uniform, rigid, while the outer tube has a sinusoidal wave traveling down its wall. The flow is investigated in a wave frame of reference moving with velocity of the wave. Numerical calculations are carried out for the pressure rise and frictional forces. The features of the flow characteristics are analyzed by plotting graphs and discussed in detail.     

Application of stain-etched porous silicon in light emitting diodes and solar cells

Porous silicon/c-Si heterostructures have been formed by the method of stain etching.The properties of light emitting diodes (LED) and solar cells have been studied. The transport mechanism of the diode has been investigated from the current–voltage characteristics measured at different temperatures (296–380 K). A model based on multi-step tunneling of carriers at reverse and low forward bias (<1 V) and on field tunneling across a narrow barrier at higher forward bias (>1.5 V) is proposed for the LED. In the case of the solar cells the porous silicon is formed in between the fingers of the front grid contact. Application of porous silicon in solar cells results in an increase of the short-circuit current and efficiency of the cells by about 30%.     

Ultrastructural characterization of cells in primary cultures from different adult tissues of Biomphalaria tenagophila TAIM,a strain that is absolutely resistant to Schistosoma mansoni infection

The etiological agent of schistosomiasis in Brazil, Schistosoma mansoni, requires an obligatory passage through Biomphalaria snails to complete its life cycle. In these intermediate hosts, interaction with the parasite is mediated by humoral factors and hemocytes by mechanisms that are not yet fully understood. Extant studies exploring these processes are usually conducted through experimental infection of Biomphalaria with S. mansoni miracidia. Thus, tissue-derived cultures of Biomphalaria may be useful in increasing the understanding of that interaction at cellular level. However, in the absence of morphological characterization of those cells in culture, the application of such models is delayed. In the present work, we cultured different tissues of B. tenagophila, the second most important host of S. mansoni in Brazil, using a strain that is naturally and absolutely resistant to S. mansoni infection. This decision was driven by the view that this strain might be provided with the most effective response against parasite infection. Primary cultures were successfully established from nine Biomphalaria tissues and the respective cells in culture were ultra structurally described. Attention was particularly devoted to cells derived from mantle cavity and kidney tissues. Although they have been considered important centers for hemocyte production in Biomphalaria, no detailed cell characterization is available in the pertinent literature. Herein, kidney-derived cells partially shared hematoblast characteristics. Moreover, under optical microscopy, kidney cells in culture were very similar to those derived from amebocyte-producing organ (APO) cultures, which have been recently shown to be capable of eliminating S. mansoni sporocysts in vitro. Based on the close resemblance of those cultures and their anatomical proximity inside the mantle cavity, we suggest the effective participation of Biomphalaria kidney cells in hematopoiesis and in host response to S. mansoni infection.     

Global dynamics of a pipe conveying pulsating fluid in primary parametrical resonance: Analytical and numerical results from the nonlinear wave equation

The chaotic dynamics of nonlinear waves in the harmonic-forced fluid-conveying pipe in primary parametrical resonance, is explored analytically and numerically. The multiple scale method is applied to obtain an equivalent nonlinear wave equation from the complicated nonlinear governing equation describing the fluid conveyed in a pipe. With the Melnikov method, the persistence of a heteroclinic structure is shown to be satisfied and its condition is given in functional form. Similarly, for the heteroclinic orbit, using geometric analysis, a condition function of the stable manifold is derived for the orbit to return to the stable manifold from the saddle point. The persistent homoclinic structures and threshold of chaos in the Smale-horseshoe sense are obtained for the fluid-conveying pipe under both conditions, indicating how the external excitation amplitude can change substantially the global dynamics of the fluid conveyed in the pipe. A numerical approach was used to test the prediction from theory. The impact of the external excitation amplitude on the nonlinear wave in the fluid-conveying pipe was also studied from numerical simulations. Both theoretical predications and numerical simulations attest to the complex chaotic motion of fluid-conveying pipes.