Magnetically modulated therapeutic systems

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Abstract

Magnetically targeted drug delivery by particulate carriers is an efficient method of delivering drugs to localized disease sites, such as tumors. High concentrations of chemotherapeutic or radiological agents can be achieved near the target site without any toxic effects to normal surrounding tissue. Non-targeted applications of magnetic microspheres and nanospheres include their use as contrast agents (MRI) and as drug reservoirs that can be activated by a magnet applied outside the body. Historic and current applications of magnetic microspheres will be discussed, as well as future directions and problems to be overcome for the efficient and beneficial use of magnetic carriers in clinical practice. More information about the field and an extensive bibliography is available at “www.magneticmicrosphere.com.”

Section snippets

Principle 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 tumor, 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

History of magnetic targeting

Magnetic drug targeting is a young field. The surgeon Gilchrist published a seminal paper in 1956 on the selective inductive heating of lymph nodes after injection of 20–100-nm-sized maghemite particles into the lymph nodes near surgically removed cancer (Gilchrist et al., 1957). Turner and Rand combined then this radiofrequency heating method with embolization therapy (Turner et al., 1975).

Gilchrist apparently did not, however, envision that his magnetic particles could be magnetically guided

Magnetic delivery of chemotherapeutic drugs to liver tumors

The first clinical cancer therapy trial using magnetic microspheres (MMS) was performed by Lübbe et al. in Germany for the treatment of advanced solid cancer in 14 patients (Lubbe et al., 1996, Lubbe et al., 2001). Their MMS 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 MMS in the target area. However, MRI measurements indicated that more than 50% of the MMS had ended up in the

Future directions

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

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