Magnetic drug delivery for Alzheimer's disease

Atomic absorption spectroscopy has been used to characterise the magnetite incorporated into chitosan microparticles that can act as delivery agents for the Alzheimer's drug tacrine. Tacrine has notoriously low oral bioavailability and unclear efficacy but this delivery approach boosts uptake.

Alzheimer's disease is an increasingly common progressive degenerative disorder of the brain that causes a slow and debilitating decline in memory and cognition and affects behaviour deleteriously. There are an estimated 15 million sufferers worldwide. However as life expectancy in the developed world increases those numbers are set to rise.

A relatively small pharmaceutical molecule known as tacrine, 1,2,3,4-tetrahydroacridin-9-amine, acts as a reversible inhibitor of the brain enzyme cholinesterase and can be used to treat mild to moderate symptoms of Alzheimer's disease. Its mode of action is based on blocking the break down of the neurotransmitter acetylcholine, which in turn is thought to boost neuronal activity.

Barnabas Wilson, Malay Kumar Samanta, Kokilampal Perumal Sampath Kumar, and Bhojraj Suresh of the Department of Pharmaceutics at J.S.S College of Pharmacy, in Tamil Nadu, India, Kumaraswamy Santhi of the School of Pharmacy, at the Asian Institute of Medicine, Science and Technology, Malaysia, and Muthu Ramasamy of the Delhi Institute of Pharmaceutical Sciences & Research, New Delhi, India, report details of their tacrine-bearing magnetic microparticles in the Journal of Neuroscience Methods in March.

The team explains how they preparted magnetic chitosan microparticles by emulsion cross-linking. They characterised the microparticles based on process yield, drug loading capacity, particle size, in vitro release, release kinetics and magnetite (Fe₃O₄) content. Magnetite characteristics were themselves determined using atomic absorption spectroscopy. The team adds that particle size was determined using scanning electron microscopy (SEM).

In preliminary tests, the team injected the loaded microparticles intravenously while holding a suitable magnet at the target region in laboratory rodents. They then measured the concentrations of tacrine at the target and non-target organs using high-performance liquid chromatography (HPLC). Results revealed that there was a significant increase in concentration of tacrine in the brain in comparison with the free drug administered using the classical approach in controls.

"Drug targeting is the delivery of drugs to receptors or organs or any other specific part of the body to which one wishes to deliver the drug exclusively," the team explains. Paul Ehrlich first proposed the notion of what is commonly known as a "magic bullet" in the early twentieth century, and researchers have spent the intervening years developing all kinds of complexes and conjugates to carry magic bullets for a wide range of diseases.

The use of magnetite-containing particles to create a magnetic magic bullet for drug delivery is particularly attractive. Such an approach does not rely on sophisticated molecular biology skills for the targeting process. Indeed, nothing more complicated than the pull of a magnetic field is used to draw the drug carrier to the target site in a manner akin to the movement of iron filings in a child's magnetic funny face toy.

"Magnetic carrier technology was first used in the early 1940s as a new methodology in waste water treatment," the researchers point out. Medical researchers were then attracted to the idea of using suitable magnetic particles to help them deliver pharmaceuticals to specific locations in the body.

"The magnetic chitosan microparticles increased the concentrations of tacrine in the brain by 5.38 fold when compared to the free drug tacrine," the researchers explain." The developed formulations may also reduce the total dose required for the therapy with concurrent reduction in dose related toxicity," the researchers conclude.

They add that, "magnetic microparticles require further studies as a drug-delivery system including long-term toxicity studies. It is also important to optimize the magnetic field parameters and physicochemical properties of the carrier to improve site specificity."