Magnetic nanoparticles for drug delivery
By Dr. Afsaneh Motamed-Khorasani

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Targeted drug delivery is a major problem for the treatment of many diseases. Magnetic nanoparticles (MNPs) can be considered as promising drug-delivery candidates due to their special properties. They can be handled easily by an external magnetic field and can be delivered by passive and active strategies. Furthermore, visualization has become easy in MRI scans due to the use of MNP. Optimal drug doses can also be loaded on MNP due its enhanced bioavailability properties.

However, there are some drawbacks to the use of MNPs. Magnetic carriers are not always effective in achieving targets due to an inadequate magnet system. MNPs might aggregate and lose their specific properties due to their small size. Also, drugs loaded with MNPs might not always overcome the force of blood flow and thus might not reach the target site.
The use of magnetic nanoparticles makes visualization of drug delivery easy with MRI scans.

Therefore, before developing the magnetic particle-based drug delivery systems, many factors must be considered, including: magnetic properties and size of the particles, rate of the blood flow and strength of the magnetic field.

Although different types of magnetic materials such as pure metals, manganese and iron oxides are available, lack of sufficient knowledge about their toxicity in the human body restricts the use of such materials. Only iron oxide nanoparticles have been approved as drug-delivery agents by Food and Drug Administration (FDA) due to their safety in physiological conditions. Iron oxides, such as magnetite and maghemite, naturally occur in the heart, liver and spleen.

Iron oxide nanoparticles are synthesized by alkaline co-precipitation of Fe3+ and Fe2+ ions. MNP can be chemically modified by gold, dendrimers, silane or polymers. MNPs could be attached to a drug through different methods, including: covalent binding, electrostatic interactions, adsorption or encapsulation process.

Drug-loaded magnetic particles can reach the target site by active and passive mechanisms. Active mechanism is based on the MNP attachment to the ligands and attraction of these conjugates to the target-site proteins. Passive mechanism is based on the enhanced permeability inside the blood vessels and tumor retention capability. Many drugs such as ciprofloxacin, gemcitabine, doxorubicin, 5-Fluorouracil, dunorubicin, anti-b-HCG monoclonal antibody, cisplatin, paclitaxel, 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), t-PA and dopamine have been successfully targeted by using MNPs.

Multitasking treatments, which include magnetic resonance or magnetofluorescent imaging, and targeted drug delivery can improve cancer therapy. Recently, the efficiency of MNPs for in-stent thrombosis has been determined. Traditional thrombolytic therapy could be associated with complications such as severe hemorrhages. Preliminary studies indicated that MNP loaded with tissue plasminogen activator (tPA), a thrombolytic drug, can be effectively used for the treatment of the in-stent thrombosis.

The cell toxicity of MNPs coated with long-chain polymers has been shown to be less as compared to MNPs coated with short-chain polymers. Biodistribution of magnetic particles and their uptake by macrophages depends upon their size and surface chemistry. It has been determined in many studies that iron oxide nanoparticles could accumulate in tissues without much change in the organs. MNPs might induce oxidative stress in the tissues, which can ultimately lead to apoptosis and mutagenesis. So, in order to prevent an oxidative stress-induced apoptosis, an appropriate dosage of MNPs is required.

In summary, targeted drug delivery would be possible with the use of MNPs due to their unique properties. This can be achieved by conjugating MNPs with specific ligands and controlling these conjugates by an external magnetic field. Iron and gadolinium can be used as contrasting agents in MRI.

Meanwhile, the cell toxicity associated with the use of MNPs could be prevented by using appropriate dosages. Drug delivery into the organs, such as brain or stented blood vessels, could be possible with MNPs due to their magnetic cellular permeability property. Major studies are ongoing that could lead to potential novel application of MNPs in the field of medicine.

Dr. Afsaneh Motamed-Khorasani is a medical and scientific affairs specialist with a strong background in biomedical sciences, clinical trial/research and medical/regulatory writing/submission. She is the president and managing director of Neometrix Consulting Inc., which helps global pharmaceutical and medical device companies with their medical and regulatory writing and submissions as well as medical affairs.