INTRODUCTION:

Drug targeting is the delivery of drugs to receptors or organ or any other specific part of the body to which one wishes to deliver the drug exclusively. Delivery of drugs is an important component of the treatment of diseases both from a commercial and a scientific point of view, as the method by which a drug is delivered can have a significant effect on its efficacy. Scientifically, it is extremely challenging, as the goal is to find a drug-delivery system with the capability for site-specificity as well as controlled release¹.

Magnetic Drug Targeting means the specific delivery of chemotherapeutic agents to their desired targets, e.g. tumors by using magnetic nanoparticles (ferrofluids) bound to these agents and an external magnetic field which is focused on the tumor. This type of target directed drug injection attempts to concentrate a pharmacologic agent by enhancing its efficacy while simultaneously minimizing deleterious side effects².

ADVANTAGES OF MAGNET TARGETING:³

Magnetic targeting has several advantages, which includes:

· Therapeutic responses in the target organs at only one tenth of the free drug dose.

· Controlled drug release within target issues for intervals of 30 min to 30 hrs.

· Avoidance of acute drug toxicity directed against endothelium and normal parenchymal cells.

· Adaptable to any part of the body.

· This drug delivery system reduces circulating concentration of free drug by a factor of 100 or more.

DISADVANTAGES OF MAGNET TARGETING:⁴

This novel approach suffers from certain disadvantages also as given below:-

· Magnetic targeting is an expensive, technical approach and acquires specialized manufacture and quality control system.

· Its needs specialized magnet for targeting, advanced techniques for monitoring, and trained personnel to perform procedures.

· Magnet must have relatively constant gradients, in order to avoid focal over dosing with toxic drugs.

· A large fraction (40-60%) of magnetite, which is entrapped in carriers, is deposited permanently in target tissues.

· Drug cannot be targeted to deep seated organs in the body, so this approach is confined to the targeting of drugs in superficial tissue only like skin, superficial tumour or to joints only

Principles of magnetic targeting:-

Magnetic drug delivery by particulate carriers is a very efficient method of delivering a drug to a localized disease site. Very high concentrations of chemotherapeutic or radiological agents can be achieved near the target site, such as a tumour, without any toxic effects to normal surrounding tissue or to the whole body. Fig. 1 highlights the concept of magnetic targeting by comparing systemic drug delivery with magnetic targeting. In magnetic targeting, a drug or therapeutic radioisotope is bound to a magnetic compound, injected into a patient’s blood stream, and then stopped with a powerful magnetic field in the target area.⁵ Depending on the type of drug, it is then slowly released from the magnetic carriers (e.g. release of chemotherapeutic drugs from magnetic micro-spheres) or confers a local effect (e.g. irradiation from radioactive microspheres; hyperthermia with magnetic nanoparticles). It is thus possible to replace large amounts of freely circulating drug with much lower amounts of drug targeted magnetically to localized disease sites, reaching effective and up to several-fold increased localized drug levels. Magnetic carriers receive their magnetic responsiveness to a magnetic field from incorporated materials such as magnetite, iron, nickel, cobalt, neodymium– iron–boron or samarium–cobalt. Magnetic carriers are normally grouped according to size. At the lower end, we have the ferrofluids, which are colloidal iron oxide solutions. Encapsulated magnetite particles in the range of 10–500 nm are usually called magnetic nanospheres and any magnetic particles of just below 1–100 nm are magnetic microspheres. In generals, magnetic liposome’s are also included when speaking about magnetic carriers.⁶

Fig. 1. Principle of magnetic targeting

Flowchart of principle of magnetic targeting:-

The principle of magnetic targeting by comparing systemic drug delivery with magnetic targeting. In magnetic targeting, a drug or therapeutic radioisotope is bound to a magnetic compound, injected into a patient’s blood stream, and then stopped with a powerful magnetic field in the target area. The magnetic fields are believed to harmless to biological system and adaptable to any part of the human body. Up to 60% of an injected dose can deposited and released in controlled manner in selected non reticuloendothelial organs (i.e not in liver / spleen / bone marrow).⁷

Magnetic Drug Targeting: Mechanism:

Magnetic drug delivery by particulate carriers is a very efficient method of delivering a drug to localized disease site. Magnetic drug transport technique is based on the fact that the drug can be either encapsulated into a magnetic microsphere (or nanosphere) or conjugated on the surface of the micro/nanosphere. When the magnetic carrier is intravenously administered, the accumulation takes place within area to which the magnetic field is applied and often augmented by magnetic agglomeration. The accumulation of the carrier at the target site allows them to deliver the drug locally. Efficiency of accumulation of magnetic carrier on physiological carrier depends on physiological parameters eg. Particle size, surface characteristic, field strength, and blood flow rate etc. The magnetic field helps to extravasate the magnetic carrier into the targeted area. Very high concentration of chemotherapeutic agents can be achieved near the target site without any toxic effect to normal surrounding tissue or to whole both us possible to replace large amounts of drug targeted magnetically to localized disease site, reaching effective and up to several fold increased drug levels.⁸

Fig. 2. Concept of magnetic drug targeting.

Fig.3. Various nonmagnetic micro carries (nanoparticles, microspheres and microparticles etc.) are successfully utilized for drug targeting but they show poor site specificity and are rapidly cleared off by RES (reticuloendothelial system)

Magnet design:

The force exerted by a gradient magnetic field is an important parameter that governs in magnetic targeting of microcarries. The relationship of magnetic force to field gradient and magnetic moment of particles is expressed by following equation:⁹

F = M ∆H:

Where, f is force on particles; M is magnetic movement of particles after saturation magnetism; ∆H is magnetic field gradient

This equation explains that spheres with increased magnetic moment will experience force sufficient for extra vascular migration at proportionately lower field gradients. The

Magnetic, moment of microsphere magnetic can be increased in three ways

1. By magnetizing the spheres to saturation levels prior to vascular targeting.

2. By clustering magnetite at the centre of each sphere to produces large macro domains

3. By substituting one of the newer ferromagnetic materials that as higher susceptibility than Fe₃O_4.

The acute and chronic toxicities of several new magnetic alloys must be assessed before using them in delivery devices.

Magnetically modulated microcarriers:

Magnetic microcarriers are site specific and by localization of these microcarriers in the target area, the problem of their rapid clearance by RES is also surmounted. Linear blood velocity in capillaries is 300 times less i.e.0.05cm/sec as compared to arteries, so much smaller magnetic field, 6-8 Koe, is sufficient to retain them in the capillary network of the target area¹⁰. Magnetic carrier technology appears to be a significant alternative for the bimolecular malformation (i.e. composition, inactivation or deformation).These microcarriers includes :-

A) Magnetic microsphere

B) Magnetic liposomes

C) Magnetic nanoparticles

D) Magnetic Resealed Erythrocytes

E) Magnetic Emulsion

F) Biomodulators

G) Magnetic neutrophils

A) Magnetic microspheres:

Magnetic microspheres are supramolecular particles that are small enough to circulate through capillaries without producing embolic occlusion (<4 μm) but are sufficiently susceptible (ferromagnetic) to be captured in microvessels and dragged in to the adjacent tissues by magnetic fields of 0.5-0.8 tesla (T). Magnetic microspheres were prepared by mainly two methods namely phase separation emulsion polymerization (PSEP) and continuous solvent evaporation (CSE). The amount and rate of drug delivery via magnetic responsive microspheres can be regulated by varying size of microspheres, drug content , magnetite content , hydration state and drug release characteristic of carrier. The amount of drug and magnetite content of microspheres needs to be delicately balanced in order to design an efficient therapeutic system. Magnetic microsphere are characterized for different attributes such as particle size analysis including size distribution ,surface topography, and texture etc. using scanning electron microscopy (SEM), drug entrapment efficiency, percent magnetite content, and in vitro magnetic responsiveness and drug release.¹¹

Targeting by magnetic microspheres i.e. incorporation of magnetic particles in to drug carriers (polymers) and using an externally applied magnetic field is one way to physically direct this magnetic drug carriers to a desired site, Widder first reported on the use of magnetic albumin microspheres.¹²

Fig 4. Magnetic targeting of Antitumour Microspheres to pancrease

B) Magnetic liposomes:

Liposomes are simple microscopic vesicles in which lipid bilayer structures are present with an aqueous volume entirely enclosed by a membrane, composed of lipid molecule. There are a number of components present in liposomes, with phospholipids and cholesterol being the main ingredients but in case of magneto liposomes magnetite is one of the component of the liposomes. Generally these are magnetic carrier which can be prepared by entrapment of Ferro fluid within core of liposomes^.Magneto liposome can also be produced by covalent attachment of ligands to the surface of the vehicles or by incorporation of target lipids in the matrix of structural phospholipids.¹³ Alternatively magnetoliposomes are prepared using the phospholipid vesicle as a nanoreactor for the in situ precipitation of magnetic nanoparticles. Vesicles are also prepared containing didodecyl methyl ammonium bromide; contain an ionic magnetic fluid^. These magnetoliposomes were effectively used for site specific targeting, cell sorting and as magnetic resonance contrast enhancing agent. Thermo sensitive magnetoliposomes can release the entrapped drug after selective heating caused by the electromagnetic fields.Magneto fluorescent liposomes were used for increasing sensitivity of immune fluorescence. The magneto liposomes are characterized for their physical attributes i.e. size, shape, and size distribution, surface charge, percent capture, percent magnetite content, entrapped volume lamellarity through freeze fracture microscopy and P-NMR, phase behavior drug release, quantitative determination of phospholipids and cholesterol analysis.¹⁴

C) Magnetic nanoparticles:

Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to specifically tailor the features and properties of MNPs for these biomedical applications. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. Through the incorporation of highly specific targeting agents and other functional ligands, such as fluorophores and permeation enhancers, the applicability and efficacy of these MNPs have greatly increased. This review provides a background on applications of MNPs as MR imaging contrast agents and as carriers for drug delivery and an overview of the recent developments in this area of research.¹⁵

The important properties of magnetic particles for medical applications are nontoxicity, biocompatibility, injectability and high-level accumulation in the target tissue or organ. Magnetic nanoparticles modified with organic molecules have been widely used for biotechnological and biomedical applications as their properties can be magnetically controlled by applying an external magnetic field¹⁶. Furthermore, a novel application of magnetic nanoparticles and magnetic forces for tissue engineering, termed 'magnetic force-based tissue engineering' has been proposed. Particular attention had been paid to the preparation methods that allow the synthesis of particles of nearly uniform size and shape.¹⁷

Fig 5 -Schematic representation of retaining of Magnetic nanoparticles at Rat Tail target segment

D) Magnetic Resealed Erythrocytes:

Resealed erythrocytes have various advantages as drug carriers such as it is biodegradable, biocompatible, large quantity of variety of material can be encapsulated within small volume of cell and can be utilized for organ targeting etc. Due to these advantages of resealed erythrocytes, magnetic resealed erythrocytes came in to existence which contains ferrofluides (magnetite) along with loaded drugs within the cell. Magnetically responsive ibuprofen-loaded erythrocytes were prepared and characterized in vitro. The erythrocytes loaded with ibuprofen and magnetite (ferrofluids) using the preswell technique¹⁸. The loaded cell effectively responded to an external magnetic field. Various process variables including drug concentration, magnetite concentration, sonication of ferrofluids that could affect the loading of drugs and magnetite were studied. The loaded erythrocytes were characterized for in vitro drug efflux, hemoglobin release, morphology osmotic fragility, in vitro magnetic responsiveness and percent cell recovery. In the continuous study, diclofenac sodium bearing erythrocytes were prepared by preswell technique and characterized for various in vitro parameters.¹⁹

Fig 6 - Prevention of Arterial Thrombosis by Aspirin loaded Magnetic Resealed Erythrocytes.

Thrombosis absorbed or flushed due to the Force exerted by flow of Magnetic

Erythrocytes under magnetic field, aspirin also released in vicinity of thrombosis

(Thrombolytic effect)

Local thrombosis in animal arteries was prevented by means of magnetic targeting of aspirin loaded red cell. Thrombosis was induced in 18 dogs and 16 rabbit’s arteries by surgically inverting a vascular wall flap into its lumen. A completely occluding red thrombus was developed inside the vessel after 4 to 5 hrs in 80% of cases. SmCo5 magnet was secured externally to one of the arteries. The constant magnetic field produced by the magnet had no influence on the clot formation. Autologous red cells loaded with ferromagnetic colloid compound and aspirin were administered intravenously, and completely aborted arteriothrombosis on magnet application side with no deterioratory effect on clot formation in the control artery was recorded.²⁰

E) Magnetic Emulsion:

Besides magnetic modulated systems, like microcapsules/microspheres Magnetic emulsion was also tried as drug carrier for chemotherapeutic agents. The emulsion is magnetically responsive oil in water type of emulsion bearing a chemotherapeutic agent which could be selectively localized by applying an external magnetic field to specific target site²¹.Akimoto and Morimoto prepared magnetic emulsion by utilizing ethyl oleate based magnetic fluid as the dispersed phase, casein solution as the continuous phase and anticancer agent, methyl CCNU trapped in the oily dispersed phase as active chemotherapeutic agent. Magnetic emulsion appears to have potential in conferring site specificity to certain chemotherapeutic agent.²²

F) Biomodulators:

Biological response modifiers (BMRs) alter host, tumor as well as microbial responses in four ways²³

1. Augmentation of host effectors mechanisms directed against tumor cells or micro organisms.

2. Decrease in host response that interferes with tumor resistance by a quantitative increase in endogenous effector resistance by an increase in endogenous effector molecules or redirecting their sites and duration of action.

3. Augmentation of tumor sensitivity to host cells by dedifferentiating tumor cells.

4. Increase in host tolerance of conventional cancer treatment.

There are basically two types of agents; Indirect and direct agents. Indirect agents include white cell chemo attractant / activator peptides, interleukins (1 to 4) and immunomodulators such as interferon (α, β, γ). Direct acting BMRs is the final lymphocytes effector molecules. These are exemplified by antibodies, lymphotoxin and tumor necrosis factor (TNF, also called as Cachetin).

G) Magnetic Neutrophils:

In certain clinical conditions, where patient sera contains chemotactic factor in activators and neutrophils directed inhibitors of chemotaxis , an indirect approach of targeting white cells by chemo attraction fails. These disorders include chronic lymphocytic leukemia, alcoholic cirrhosis, Crohn’s disease, haemodialysis, sarcoidosis and Hodgkin’s disease. Even though failure of chemotaxis is not observed in all patients, such conditions are life threatening. Therefore, a means of making neutrophils ingest magnetite base system ought to be developed, so that the sites of severe infection can be selectively approached for therapy²⁴.

Applications of Magnetic systems:

Magnetic drug delivery system have many application in various fields but out of these drug targeting utilizing magnetic micro carriers is very important. Some of the application of magnetically guided drug targeting especially tumor targeting along with some other application utilizing magnetic micro carriers has been summarized here²⁵.

Magnetic systems for the therapy of diseases:

Magnetic delivery of chemotherapeutic drugs to liver tumours:-

The first clinical cancer therapy trial using Magnetic microspheres (MMS) was performed by Lübbe in Germany for the treatment of advanced solid cancer in 14 patients. Their Magnetic microspheres were small, about 100 nm in diameter, and filled with 4_-epidoxorubicin. The phase I study clearly showed the low toxicity of the method and the accumulation of the Magnetic microspheres in the target area. However, MRI measurements indicated that more than 50% of the Magnetic microspheres had ended up in the liver. This was likely due to the particles’ small size and low magnetic susceptibility which limited the ability to hold them at the target organ. The startup company FeRx in San Diego developed irregularly shaped carbon-coated iron particles of 0.5–5nm in diameter with very high magnetic susceptibility and used them in a clinical phase I trial for the treatment of inoperable liver cancer. They have treated 32 patients to date and are able to super-selectively (i.e. well directed) infuse up to 60 mg of doxorubicin in 600 mg Magnetic microspheres with no treatment-related toxicity. The firm recently started a large phase I/II trial for the treatment of hepatocellular carcinoma in China, Korea, and the US. Current preclinical research is investigating the use of magnetic particles loaded with different chemotherapeutic drugs such as mitoxantrone, mitomycin C, etoposide, paclitaxel or oxaliplate. In case of brain tumors, the therapeutic ineffectiveness of chemotherapy is mainly due to the impervious nature of the blood-brain barrier (BBB), presence of drug resistance and lack of tumor selectivity. Various novel biodegradable magnetic drug carriers are synthesized and their targeting to brain tumor is evaluated in vitro and in animal models. New cationic magnetic amino dextran micro spheres (MADM) have been synthesized. Its potentiality for drug targeting to brain tumor was studied. This particle were retained in brain tissue over a longer period of time. In one of such examples magnetic doxorubicin in liposome, significant anticancer effect in nude mice bearing colon cancer²⁶.

Magnetic bioseparation:

Bioseparation is an important phenomenon for the success of several biological processes. Therefore, prospective bioseparation techniques are increasingly gaining importance. Amongst the different bioseparation techniques, magnetic separation is the most promising. The development of magnetically responsive microspheres has brought an additional driving force into play. Particles that are bound to magnetic fluids can be used to remove cells and molecules by applying magnetic fields and-in vivo-to concentrate drugs at anatomical sites with restricted access. These possibilities form the basis for well-established biomedical applications in protein and cell separation. Additional modifications of the magnetic particles with monoclonal antibodies, lectins, peptides, or hormones make these applications more efficient and also highly specific. The isolation of various macro molecules such as enzymes, enzyme inhibitors, DNA, RNA, antibodies and antigens etc. from different sources including nutrient media, fermentation broth, tissues extracts and body fluids, has been done by using magnetic absorbents. In case of enzyme separation, the appropriate affinity ligands are immobilized on polymer coated magnetic carrier or magnetizable particles. Immobilized protein A or protein G on silanized magnetite and fine magneto tactic bacteria can be used for isolation and purification of Ig G. Mono sized super paramagnetic particles, Dyna beads, have been used in isolation of mRNA, genomic DNA and proteins²⁷.

Magnetically induced Hyperthermia for treatment of cancer:

Heat treatment of organs or tissues, such that the temperature is increased to 42–46⁰C and the viability of cancerous cells reduces, is known as hyperthermia. It is based on the fact that tumor cells are more sensitive to temperature than normal cells. In hyperthermia it is essential to establish a heat delivery system, such that the tumor cells are heated up or inactivated while the surrounding tissues (normal) are unaffected.

a) Intracellular hyperthermia:

The alternative approach is to use fine particles as heat mediators instead of needles or rods such that hyperthermia becomes noninvasive. When fluids containing submicron-sized magnetic particles (typically 1–100nm) are injected, These particles are easily incorporated into the cells, since their diameters are in the nanometer range. These magnetic particles selectively heat up tissues by coupling AC magnetic field to targeted magnetic nano particles. As a result, the whole tumor can be heated up uniformly. This is called intracellular hyperthermia. It has been shown that malignant cells take up nine times more magnetic nano particles than normal cells. Therefore the heat generated in malignant cells is more than in normal cells. Also, as blood supply in the cancerous tissues is not normal, the heat dissipation is much slower. Hence, the temperature rise in the region of tumor is higher than in the surrounding normal tissues. It is therefore expected that this therapy is much more concentrated and localized²⁸.

b) Magnetic fluid hyperthermia (MFH):

Magnetic fluids can be defined as fluids, consisting of ultramicroscopic particles. (~100Å) of magnetic oxide. Magnetic fluid hyperthermia is based on the fact that sub domain magnetic particles produce heat through various kinds of energy losses during application of an external AC magnetic field. If magnetic particles can be accumulated only in the tumor tissue, cancer specific heating is available, various biocompatible magnetic fluids. Cationic magnetoliposomes and affinity magnetoliposomes have been used for hyperthermia treatment²⁹.

c) Combination therapy:

There also exists the combination therapy which would induce hyperthermia treatment followed by chemotherapy or gene therapy. A combination of chemotherapy or radiation therapy with hyperthermia is found much more effective than hyperthermia itself. The approach involves use of magnetic carriers containing a drug to cause hyperthermia using the standard procedure, followed by the release of encapsulated drug that will act on the injured cells. It is anticipated that the combined treatment might be very efficient in treating solid tumor. Several reasons are given for the enhanced effect. Tumors are poorly vascularised and it can be hard for therapeutic agents to reach their target. Heat increases the perfusion of a tumor and therefore drugs are transported more effectively into the target tissues. In addition, heat makes blood vessels more permeable to drugs. This occurs preferentially in tumors where blood vessels tend to be structurally incomplete. On the other hand, normal blood vessels are surrounded by a basement membrane and other perivascular cells and not significantly affected by heat. It has recently been reported that hyperthermia increases the rate of liposome leakage into tumors by a factor of 2–5 depending on the type of tumor. In normal tissues however, enhancement of liposome leakage is not reported. The magnetic component in microspheres can also be used for purposes other than targeting. Langer et al. embedded magnetite or iron beads into a drug-filled polymer matrix and then showed that they could activator increase the release of the drug from the polymer by moving a magnet over it or by applying an oscillating magnetic field. The micro-movement within the polymer seemed to have shaken the matrix or produced “micro-cracks,” and thus made the influx of liquid, dissolution and efflux of the drug possible. In this way, it was possible to magnetically activate the release of insulin from a depot underneath the skin. Done repeatedly, this would allow for pulsatile drug delivery³⁰.

Fig.7. Magnetic control of pharmacokinetic parameter rand Improvement of Drug releases

Magnetic targeting of radioactivity:

Magnetic targeting can also be used to deliver therapeutic radioisotopes. The advantage of this method over external beam therapy is that the dose can be increased, resulting in improved tumor cell eradication, without harm to nearby normal tissue. Different radioisotopes can treat different treatment ranges depending on the radioisotope used—the emitters 90Y for example will irradiate up to a range of 12mm in tissue. Unlike chemotherapeutic drugs, the radioactivity is not released, but rather the entire radioactive microsphere is delivered to and held at the target site to irradiate the area within the specific treatment range of the isotope. Once they are not radioactive anymore, biodegradation of the microspheres occurs (and is desired). Initial experiments in mice showed that intra peritoneally injected radioactive poly lactic acid based MMS could be concentrated near a subcutaneous tumor in the belly area, above which a small magnet had been attached³¹. The dose-dependent irradiation from the emitter 90Y-containing MMS resulted in the complete disappearance of more than half of the tumors. Magnetic targeted carriers (MTC; from FeRx), which are more magnetically responsive iron carbon particles, have been radio labelled in the last couple of years with isotopes such as 188Re , 90Y, 111In and 125I and are currently undergoing animal trials³².

Miscellaneous Applications:

The most important application of magnetic particles is as contrast agent for magnetic resonance imaging in diagnosis of diseases. The most commonly used super paramagnetic material is Fe₃O₄ with different coatings such as dextrans, polymers, and silicone. Supra magnetic iron oxide (SPIO) it has been mainly used as a liver-specific contrast agent for intravenous application. It may also be used for detection of metastases in non-enlarged lymph nodes. Magnetic elements have been successfully used in gastrointestinal surgery for tissue fixation. Which form hermetic seal after surgery and passibility of the gastrointestinal tract is maintained and the patient can able to eat immediately after operation. Magnetically guided ferro fluid nanoparticles were used in retinal repair. Magnetically guided interstitial diffusion of the nanoparticles up to 20mm of the gel over periods of 72 hours was shown to be possible, thus demonstrating that essentially all points on the retinal surfaces are reachable from elsewhere in the ocular interior. Apart from their application in drug delivery, magnetism have sound applications in biosciences and biotechnologies like immobilization, detection of biologically active compound and xenobiotic, detection, isolation and study of cells and cells organelles. Similar to chemotherapeutic drugs, many other drugs including peptides and proteins can be adsorbed or encapsulated into magnetic microspheres or nanospheres. Normal pharmaceutical technology is employed to influence release kinetics. Ongoing work describes the encapsulation of the peptide octreotide and the protein tumor necrosis factor alpha (TNF). A very recent development in the field of magnetic targeting is the use of magnetically enhanced gene therapy. Advantages of such an approach are targeted gene transfection at rapid speed and high efficiencies. It is also possible to use only the mechanical-physical properties of magnetic particles or ferrofluids for therapy. One example is the embolization (clogging) of capillaries under the influence of a magnetic field. In this way, tumors could be specifically starved of their blood supply. Another elegant example is the use of magnetic fluids to prevent retinal detachment, thus preventing the patients from going blind. A magnetized scleral buckle, similar to a rubber band, is placed around the eye. The magnetic fluid is then injected into the eye and immediately drawn towards the buckle by its magnetic forces³³.

Magnetic systems for the diagnosis of diseases:

The most important diagnostic application of magnetic nanospheres is as contrast agents for magnetic resonance imaging (MRI). Saini tested 0.5–1 _m sized ferrites in vivo for the first time in 1987. Since then, smaller super paramagnetic iron oxides (SPIOs) have been developed into unimodular nanometer sizes and have since 1994 been approved and used for the imaging of liver metastases (ferumoxide based Feridex I.V., or Endorem in Europe) or to distinguish loops of the bowel from other abdominal structures (GastroMark, or Lumirem in Europe) ³⁴.

Magnetic systems for magnetic cell separation:

The era of using magnetic particles with surface markers against cell receptors started in 1978. Currently, many different kits for the sample preparation, extraction, enrichment and analysis of entire cells based on surface receptors, and subcellular/molecular components such as proteins, mRNA, DNA are available. Analytical procedures, such as many different immunoassays, are often based on magnetic separation. More information is available from the firms providing these kits, such as Dynal, Miltenyi, Bangs Laboratories, micromod. One important application of magnetic cell separation is the purging of malignant cells from auto logous stem cell products, depletion of T cells, and selection of specific lymphocyte subsets with potential antileukemic activity. In this way, a cancer patient’s stem cells can be extracted, purified, and then injected again after he has gone through a harsh cancer. The therapeutic applications of immune magnetic cell selection are based on antibodies that bind to cancer cell antigens such as CD10, CD19 or CD20. Two machines for magnetic cell separation have recently received FDA approval, Cellpro’s “Ceprate SC stem cell collection system” and Baxter’s “Isolex 300I.” A third system is approved in Europe, Miltenyi’s “ClinicMACS” system³⁵.

Magnetic Systems in Contraceptive Drug Delivery

In these magnetically controlled systems, the drug and small magnetic beads are uniformly dispersed within a polymer material. On exposure to aqueous media, the drug is released in a diffusion controlled fashion. Moreover, the rate can be increased or modulated on application of an oscillating external magnetic field (Robinson and Lee, 1987). These system may be useful when drug delivery is designed responsive to the changes in steroid secretion during the menstrual cycle³⁶.

Future Perspectives:-

Conceptually, magnetic targeting is a very promising approach. However, there are a number of physical, magnetism-related properties which require careful attention. First, the magnetic force, which is defined by its field and field gradient, needs to be large and carefully shaped to fit the target area. For in vivo applications, this is not trivial, and collaborations with electrical or biomedical engineers are advisable. Second, the magnetic susceptibility of the MMS needs to be as high as possible. More responsive magnetic materials of defined and homogeneous material properties in a (tissue) stable and defined oxidation state need to be synthesized. Third, the MMS size must be small enough that they do not clog the blood vessels through which they are guided to the target organ. In cases where it may be desirable to circulate particles through the body rather than injecting them in close proximity to the treatment area, additional benefits are obtained if the particles are small enough to minimize their trapping in other organs such as the lungs or liver. Fourth, altering the surface of MMS with appropriate molecules should always be considered to either decrease the interaction of MMS with tissues or organs, using for example PEG; or to specifically bind to target cell populations using for example antibodies or receptor agonists. Finally, the MMS size must be uniform enough to provide an equal probability of magnetic capture for each MMS and constant drug/radioactivity content. Beside the magnetic properties, the fate of the particles in the body is an important consideration both for local and systemic short- and long-term toxicity. Furthermore, the pharmacokinetic characteristics must be optimized for the specific target organ, taking into account that the normal organ behaviour might differ from that of a diseased organ³⁸.

CONCLUSION:-

Magnetic Vesicular systems have been realized as extremely useful carrier systems in various scientific domains. Over the years, magnetic microcarriers have been investigated for targeted drug delivery especially magnetic targeted chemotherapy due to their better tumor targeting, therapeutic efficacy, lower toxicity and flexibility to be tailored for varied desirable purposes. In spite of certain drawbacks, such as strong magnetic field requires for the ferrofluid and deposition of magnetite the magnetic microcarriers still play an important role in the selective targeting, and the controlled delivery of various drugs. It is a challenging area for future research in the drug targeting so more researches, long term toxicity study, and characterization will ensure the improvement of magnetic drug delivery system.

Magnetically modulated drug release from implants, successfully compensate any decay in drug release against time. Moreover, it minimizes the cost, size and complexity of implanted devices. However, utility of such implants has been compromised due to irreproducibility of magnetic modulation and necessity of surgery to replace such implants after complete drug release. Externally programmable infusion pump, need magnetic modulation only to a limited extent for activating radiometry circuits to allow bi-directional information transfer. These pumps are potentially useful and exhibit the flexibility required in the complex clinical applications of the forthcoming future.

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Received on 18.09.2011 Modified on 25.09.2011

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