Magnetic Drug Delivery System Research Articles

Self-assembled magnetic liposomes from electrospun fibers

A new and facile route for preparing magnetic liposomes from electrospun fibers comprising the hydrophilic polymer polyvinylpyrrolidone K90, phosphatidyl choline and Fe3O4 nanoparticles is reported. The composite fibers were found to contain Fe3O4 particles dispersed relatively uniformly. Magnetic liposomes formed spontaneously via molecular self-assembly when the composite fibers were added to water. The liposomes were found to be generally well dispersed, and stable to degradation. Their size can be controlled by varying the Fe3O4 content of the fibers. The magnetic properties of the nanoparticles are maintained through the electrospinning and self-assembly processes, indicating that these materials maybe have very considerable potential in the development of magnetic drug delivery systems and other therapeutic or theranostic applications.

Computational modeling of magnetic nanoparticle targeting to stent surface under high gradient field

A multi-physics model was developed to study the delivery of magnetic nanoparticles (MNPs) to the stent-implanted region under an external magnetic field. The model is firstly validated by experimental work in literature. Then, effects of external magnetic field strength, magnetic particle size, and flow velocity on MNPs' targeting and binding have been analyzed through a parametric study. Two new dimensionless numbers were introduced to characterize relative effects of Brownian motion (BM), magnetic force induced particle motion, and convective blood flow on MNPs motion. It was found that larger magnetic field strength, bigger MNP size, and slower flow velocity increase the capture efficiency of MNPs. The distribution of captured MNPs on the vessel along axial and azimuthal directions was also discussed. Results showed that the MNPs density decreased exponentially along axial direction after one-dose injection while it was uniform along azimuthal direction in the whole stented region (averaged over all sections). For the beginning section of the stented region, the density ratio distribution of captured MNPs along azimuthal direction is center-symmetrical, corresponding to the center-symmetrical distribution of magnetic force in that section. Two different generation mechanisms are revealed to form four main attraction regions. These results could serve as guidelines to design a better magnetic drug delivery system.

Characterization and dielectric properties of magnetic nanoparticles (Ferrofluid) conjugated with chemotherapy drug for medical application

Basically, magnetic drug delivery system using magnetic nanoparticle carriers targeted by an external magnetic field has been recently a promising choice to avoid problems coupled with usual chemotherapy. An external magnetic field is used to localize the drug loaded carriers at the tumor site and the drug can then be released from the carriers. Consequently, our study is concerned with the ferrofluid (Fe3O4) as magnetic nanoparticles coated with PEG (polyethylene glycol) and conjugated with the doxorubicin as an anti-cancer drug in which the doxorubicin mixed with different four amounts of ferrofluid 700,800,900 and 1100 µl respectively. Herein, characterization of the ferrofluid (Fe3O4) were carried out using x- ray. Transmission electron microscope (TEM) technique was used for all the mixed samples to define the shape of conjugation. FT-IR method was used in wave number range from 400 to 4000 cm -1 to characterize the structure of the samples. Moreover, the dielectric properties of the samples, such as dielectric constant, ', dielectric loss '' and AC conductivity, for these prepared samples were investigated in the frequency range from 0.5 kHz to 1MHz at 25±1 o C. Our study has been extended to include measurements of absorption spectrum of the samples in wave length range from 300 to 900 nm. The results showed that the samples were characterized by three peaks at wave numbers 490, 1637 and 3459 cm -1 by using FT-IR method. In addition to that TEM technique explained the shape of conjugation of doxorubicin with ferrofluid. Ferrofluid spread on DOX and caused increasing in the darkening of the film due to increasing of their amounts. Also, the conductivity of the samples changed with increasing the ferrofluid amounts. Both of the dielectric constant, ' and dielectric loss '',, showed slight changes. The absorption peaks of the samples increased with increasing the ferrofluid amounts loaded with the doxorubicin and the absorption bandwidth became broader.

Magnetic and pH sensitive drug delivery system through NCA chemistry for tumor targeting

Magnetic- and pH- dually sensitive drug delivery system.

Multifunctional SBA-15 for magnetically oriented and pH targeted delivery of ibuprofen

A magnetic and pH targeting drug delivery system based on the magnetic nanocomposite doping mesoporous silica material has been successfully prepared. The material exhibited highly ordered mesostructure, large Brunauer–Emmett–Teller surface area, high pore volume, regular nanoparticle morphology and superior magnetic property. The structure and properties of the magnetic mesoporous nanocomposites were characterised by X-ray diffraction, scanning electron microscope, transmission electron microscope, N2 adsorption–desorption, Fourier transform infrared spectroscopy and vibrating sample magnetometer technique. The as obtained magnetic mesoporous material was used as drug carrier, and ibuprofen was used as model drug. The releases in simulated proximal intestine fluid (pH 7·4) and simulated gastric fluid (pH 1·2) were studied. Therefore, a novel multifunctional drug delivery system with magnetically oriented and alkalescence site targeted release has been obtained.

Radiation synthesis of magnetic sensitive ferrogels from poly(ethylene glycol) and methacrylic acid as drug delivery matrices for vitamin B12

In this work, magnetic sensitive hydrogel (ferrogel) was prepared by gamma irradiation of poly(ethylene glycol) (PEG)/ methacrylic acid (MAc) blends in the presence of Fe3O4 particles. The release of vitamin B12 from ferrogels was studied in the absence of magnetic field (MFOFF) and under switching magnetic field (MFON). Different parameters such as effect of MAc ratio, temperature, pH and magnetic field on swelling and the release characters of vitamin B12 were investigated. The PEG/MAc ferrogels displayed magnetic sensitivity, in which the release of vitamin B12 increased greatly under switching magnetic field. The permeability coefficient (P) was calculated. The results suggested that this type of ferrogels may be considered as magnetic sensitive drug delivery systems.

Construction of a Novel Magnetic Targeting Anti-Tumor Drug Delivery System: Cytosine Arabinoside-Loaded Bacterial Magnetosome.

To ease the side effects triggered by cytosine arabinoside (Ara-C) for acute leukemia treatment, a novel magnetic targeting anti-tumor drug delivery system was constructed through bacterial magnetosomes (BMs) from Magnetospirillum magneticum AMB-1 combined with Ara-C by crosslinking of genipin (GP). The results showed that Ara-C could be bonded onto the membrane surface of BMs effectively through chemical crosslinking induced by dual hand reagents GP. The average diameters of BMs and Ara-C-coupled BMs (ABMs) were 42.0 ± 8.6 and 72.7 ± 6.0 nm respectively, and the zeta potentials (−38.1 ± 9.1) revealed that these systems were stable, confirming the stability of the system. The optimal encapsulation efficiency and drug loading were 89.05% ± 2.33% and 47.05% ± 0.64% respectively when crosslinking reaction lasted for 72 h. The system also presented long-term stability and release behaviors without initial burst release (Ara-C could be released 80% within three months). Our results indicate that BMs have great potential in biomedical and clinical fields as a novel anti-tumor drug carrier.

Precise Control of the Drug Kinetics by Non-Invasive Magnetic Drug Delivery System

To solve the problems of side effects and medicinal lowering, studies on the magnetic drug delivery system (MDDS) have been applied. MDDS is a technique to accumulate drugs by using magnetic force as the physical driving force. It is necessary to apply a strong external magnetic field and high magnetic gradient to accumulate the ferromagnetic drugs to a deep diseased part noninvasively. However, by applying a static magnetic field from one direction, the drug accumulates only at the body surface near the magnet. In this study, we proposed a new method of MDDS in which a high-temperature superconducting (HTS) bulk magnet rotates around a target part. First, the particle trajectory simulation was conducted to examine the drug kinetics in a capillary blood vessel under the condition of rotating a magnet. Based on the results, the accumulation experiments of ferromagnetic particles with model blood vessels were conducted. As a result, the accumulation possibility of the ferromagnetic particles in the deep targeted part of the body was confirmed.

Biocompatible Magnetic Hollow Silica Microspheres for Drug Delivery

A simple method for the synthesis of magnetic hollow silica microspheres is reported. Magnetic hollow silica was obtained after pretreating via precipitation method of the dextran template microspheres with magnetite. Silica shell was obtained from Na2SiO3. After thermal decomposition of the dextran template, the magnetic silica shells remained intact, as demonstrated by SEM and no evidence of dextran remnants was found according to FT-IR spectra. XRD patterns showed the formation of well-crystallized Fe3O4 and Fe2O3, even if the silica presence can be identified by FT-IR, XRD spectrum do not exhibit the formation of SiO2 network because of the very low degree of cristallinity. This material has been prepared in order to develop a magnetic drug delivery system that can be used to facilitate the targeted drug delivery of antibiotics, by testing the comparative antimicrobial activity of antibiotics themselves as well as loaded into the magnetic hollows against the suspended microbial cells. Citotoxicity studies have been carried on for the new materials by using tripan blue staining technique and eukaryotic cell cycle analysis. The obtained magnetic hollows proved to exhibit low citotoxicity levels on the HCT8 standardized cell line. The antimicrobial susceptibility assay revealed an improvement of the antimicrobial activity of the tested antibiotics on S. aureus, but not on E. coli strain. These results are demonstrating the potential use of the obtained microspheres as biocompatible antibiotic delivery and/or controlled release systems with. However, their efficiency seems to be dependent on the antibiotic structure as well as on the tested microbial strain.

Magnetic nanoparticle drug delivery systems for targeting tumor

Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

Magnetic nanoparticles for multi-imaging and drug delivery.

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed.

Facile fabrication of high performances MTX nanocomposites with natural biomembrane bacterial nanoparticles using GP

A novel magnetic targeting anti-tumor drug delivery system was constructed with bacterial magnetosomes (BMs) from Magnetospirillum magneticum AMB-1, which have natural magnetic iron oxide and enveloped by natural lipid bi-membrane. Methotrexate (MTX) was loaded on the BMs membrane using genipin (GP). The average particle size was 44.4±1.5nm and this system showed high drug loading (43.3–49.6%), high encapsulation efficiency (76.5–98%), and long-term release behaviors (over two months) without initial burst release to low molecule drug MTX. The method was simple but very efficient, and the results indicated that the new carrier exhibited a great potential for application in drug delivery with excellent performances for long-term release.

Development and characterization of size controlled polymeric microcapsules loaded with superparamagnetic nanoparticles

AbstractBiocompatible polymeric microcapsules encapsulated Fe3O4 nanoparticles were fabricated by double emulsion solvent evaporation method. Magnetic nanoparticles were synthesized by coprecipitation of iron oxide. scanning electron microscopy, transmission electron microscope, fourier transform infrared spectroscopy, X‐ray diffraction spectroscopy, and vibrating sample magnetometer were used to determine the morphology, structure, crystallinity, and saturation magnetization of the microcapsules, respectively. The results indicate that the composite microcapsules have nitrogen gas in the core, Fe3O4 in the internal cavity with mean diameter of 3.6 μm. Thus, the alcohol as additive was applied to control the average size and size distribution of the microcapsules. Laser particle analyzer measurements indicate that the average size and size distribution decrease with the increasing of alcohol concentration, additionally the size and size distribution increase at higher alcohol concentration. Moreover, the prepared magnetic microcapsules with the coating of polymer have superparamagnetic behavior. Furthermore, the size controlled polymeric composite microcapsules have potential to act as ultrasound contrast agents and magnetic triggered drug delivery system. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers

Tumor-targeted drug delivery systems based on supramolecular interactions between iron oxide–carbon nanotubes PAMAM–PEG–PAMAM linear-dendritic copolymers

New hybrid nanostructure-based magnetic drug delivery systems (HNMDDSs) consisting of carbon nanotubes, magnetic iron oxide nanoparticles, and linear-dendritic copolymers linked to anticancer drugs were synthesized and characterized. Polyamidoamine–polyethylene glycol–polyamidoamine (PAMAM–PEG–PAMAM) ABA type linear-dendritic copolymers were used to solubilize and functionalize carbon nanotubes through supramolecular chemistry. There are three key features of HNMDDSs: (a) use of functionalized MWCNTs as a biocompatible platform for the delivery of magnetic iron oxide nanoparticles, therapeutic drugs, and diagnostics, (b) use of PAMAM–PEG–PAMAM linear-dendritic copolymers as water soluble, biocompatible and high functional hybrid materials with a linear polyethylene glycol part which cause a high solubility for MWCNT through supramolecular interactions and dendritic PAMAM parts which cause a high functionality for MWCNT, (c) use of magnetic iron oxide nanoparticles as targeting, imaging, or hyperthermia cancer treatment agents. To prove the efficacy of synthesized HNMDDSs, they were subjected to the receptor-mediated endocytosis and release inside the cancer cells. Then, it was unambiguously proved that these tumor-targeting HNMDDSs are promising systems for future cancer therapy with low drug doses, thereby forming a solid foundation for further investigation and development. Multi-functional hybrid nanomaterials are promising systems to deliver anticancer agents to tumors. .

Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

A magnetic mesoporous silica nanoparticle-based drug delivery system for photosensitive cooperative treatment of cancer with a mesopore-capping agent and mesopore-loaded drug

Lately, there has been a growing interest in anticancer therapy with a combination of different drugs that work by different mechanisms of action, which decreases the possibility that resistant cancer cells will develop. Herein we report on the development of a drug delivery system for photosensitive delivery of a known anticancer drug camptothecin along with cytotoxic cadmium sulfide nanoparticles from a magnetic drug nanocarrier. Core-shell nanoparticles consisting of magnetic iron-oxide-cores and mesoporous silica shells are synthesized with a high surface area (859 m(2) g(-1)) and hexagonal packing of mesopores, which are 2.6 nm in diameter. The mesopores are loaded with anticancer drug camptothecin while entrances of the mesopores are blocked with 2-nitro-5-mercaptobenzyl alcohol functionalized CdS nanoparticles through a photocleavable carbamate linkage. Camptothecin release from this magnetic drug delivery system is successfully triggered upon irradiation with UV light, as measured by fluorescence spectroscopy. Photosensitive anticancer activity of the drug delivery system is monitored by viability studies on Chinese hamster ovarian cells. The treatment of cancer cells with drug loaded magnetic material leads to a decrease in viability of the cells due to the activity of capping CdS nanoparticles. Upon exposure to low power UV light (365 nm) the loaded camptothecin is released which induces additional decrease in viability of CHO cells. Hence, the capping CdS nanoparticles and loaded camptothecin exert a cooperative anticancer activity. Responsiveness to light irradiation and magnetic activity of the nanocarrier enable its potential application for selective targeted treatment of cancer.

Synthesis, Characterization and Potential Applications of Multifunctional PEO-PPOPEO- Magnetic Drug Delivery System

Magnetic nanocomposites (MNCs) have highly been acknowledged in the diagnostics and therapeutic applications. Particularly, the multifunctional MNCs have brought a variety of possibilities in targeted drug delivery as well as non-invasive multimodality imaging. A temperature-responsive magnetic drug delivery system has been developed which is made up of superparamagnetic iron oxide nanoparticles (SIONPs) core and Pluronic shell. The magnetic cores composed of congo red conjugated to SIONPs have been proved beneficial as multimodal imaging agents, while superparamagnetic properties facile conducting the nano or micro systems to the vicinity of targeted tissue. Polymer shell formed by stimuli-responsive Pluronic F127 poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) PEO-PPO-PEO block copolymer serves as the carrier for both hydrophilic and hydrophobic drugs. X-ray diffraction (XRD) and high-resolution transmission electron microscope (HR-TEM) were used to characterize as-synthesized MNCs. Furthermore, vibrating magnetometer experiments showed MNCs having a higher magnetization value than bare magnetic nanoparticles (MNPs) and easy to conduct with an external magnetic field. The hydrodynamic size of MNCs was found to be varying in response to the stimuli temperature. Once the temperature increased, the hydrodynamic radius of MNCs decreased. In addition, the feasibility of the system as a targeted drug delivery system for Alzheimer's diseases (AD) diagnosis and therapy was studied. Searching for reliable targeting molecule, recent approaches for identification of amyloid-β (Aβ) and its derivatives have been evaluated. Consequently, the amyloid-derived diffusible ligands antibodies (anti-ADDLs) have been nominated as potential targeting molecules which can be attached to the MNCs system. The possibility of anti-ADDLs conjugation to DDS has been found promising for the multifunctional drug delivery system for AD diagnosis and therapy. However, further experimental studies are required to assess the performance of the proposed DDS.

Study on Magnetic Drug Delivery System Using HTS Bulk Magnet

In this report, MDDS (Magnetic Drug Delivery System) which is a technology to control the drugs kinetics from outside the body by the magnetic field of a HTS (high temperature superconducting) bulk magnet was investigated. Liposome composed of phospholipid bilayer membrane was used as a drug carrier, in which the ferromagnetic particle and the model drug were encapsulated together. The liposomes with magnetism (magnetite-liposomes) were injected into the blood vessel, and then accumulated locally to the affected area by the strong external magnetic field generated by HTS bulk magnet. To determine the appropriate diameter of liposomes and the number of encapsulated ferromagnetic particles which can be controlled by external magnetic force, accumulation of magnet-liposome in the blood vessel was investigated with the particle trajectories simulation. Based on the result of simulation, an experimental accumulation and controlled release with simulated organ was conducted. As a result, accumulation of magnet-liposome in the simulated organ was observed, and the validity of the simulation result was confirmed.

Materials process and applications of single grain (RE)–Ba–Cu–O bulk high-temperature superconductors

This paper reviews recent advances in the melt process of (RE)–Ba–Cu–O [(RE)BCO, where RE represents a rare earth element] single grain high-temperature superconductors (HTSs), bulks and its applications. The efforts on the improvement of the magnetic flux pinning with employing the top-seeded melt-growth process technique and using a seeded infiltration and growth process are discussed. Which including various chemical doping strategies and controlled pushing effect based on the peritectic reaction of (RE)BCO. The typical experiment results, such as the largest single domain bulk, the clear TEM observations and the significant critical current density, are summarized together with the magnetization techniques. Finally, we highlight the recent prominent progress of HTS bulk applications, including Maglev, flywheel, power device, magnetic drug delivery system and magnetic resonance devices.

Precise control of the drug kinetics by means of non-invasive magnetic drug delivery system

In order to solve the problems of the side effects and medical lowering, has been advanced a study on the drug delivery system (DDS) to accumulate the drugs locally in the body with minimum dosage. The DDS is a system that controls the drug kinetics in the body precisely and accumulates the drug locally at the target part, keeping the drugs at high density. Among the DDS, the magnetic drug delivery system (MDDS) is the one that we studied. This is a technique to accumulate drugs by using the magnetic force as the physical driving force. Our previous researches showed the possibility of the technique of MDDS to accumulate the drugs with higher accumulation rate and locality than the traditional methods. It is necessary to apply a strong external magnetic field and a high magnetic gradient to accumulate the ferromagnetic drugs at a deep diseased part non-invasively. However, by applying a static magnetic field from one direction, the drug accumulates only at the surface of the body locates near the magnet. In this study, we tried to change the magnetic field applied by a superconducting bulk magnet with time, in order to make a constant and strong magnetic field applied in the center of the body and to accumulate the ferromagnetic drugs at the deep target part in the body.First of all, the effect of the surface treatment of the ferromagnetic drugs to prevent its absorption in the normal tissue was examined. Then, to increase the accumulation rate of the ferromagnetic drugs at the target part, the distribution of magnetic field was changed, and the optimum spatial and temporal conditions of magnetic field were examined.