illustration of nanoparticles


August 6, 2014

Taking pain relief in pill form is not ideal for the 1 in 4 adults who suffer with chronic pain. Ingesting medication for pain and other conditions in this way means it goes to the whole body, and often comes with side effects. Now it may be possible to overcome this problem using a new method based on nanotechnology that delivers the drug incrementally in the part of the body that needs it, for up to a year.

Writing in the Proceedings of the National Academy of Sciences, the developers describe the work they are doing to refine the technique, which uses a biodegradable nanoscale thin film laden with drug molecules that are absorbed in the body in a steady dose.

Co-author Paula Hammond, the David H. Koch Professor in Engineering at Massachusetts Institute of Technology (MIT), says it has not been easy to develop something that can release a drug for more than a couple of months, but now they are looking to create “an extremely thin film or coating that’s very dense with a drug, and yet releases at a constant rate for very long time periods.”

An internal drug delivery system that does not have to be recovered when spent

Normally, for long-term drug release, you would need to insert a reservoir or device for holding the drug back, and this is usually something non-degradable, that has to be retrieved when the dose is exhausted.


The developers suggest the multilayered film can be applied onto biodegradable nanoparticles that are then injected directly into the part of the body that needs the medication.

But the team thinks with their technique, which uses biodegradable film, you could implant it and it would release the drug for about a year, and you would not have to go in and retrieve it – it would simply biodegrade.

In their paper, the developers describe how the duration of controlled-release is significantly longer with their refined technique than that achieved by most commercially available biodegradable products.

To get the technique right, the team had to tackle a difficult problem in localized drug delivery: how to ensure that the process through which the drug is released occurs at the right pace.

They had to come up with a mechanism that limits the rate of hydrolysis – the process where water in the body breaks down the bonds that hold the drug in place and releases it into the target tissue.

Too much hydrolysis would release too much drug too quickly. The mechanism needs to allow the drug to be released in steady increments.

Drug is secured between layers of thin-film coating

The solution they developed uses a “layer-by-layer” technique that secures the drug between layers of thin-film coating.

In their paper, they describe how they tested the idea using diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) that is often prescribed for osteoarthritis and other pain or inflammatory conditions.

They bound the NSAID to thin layers of poly-L-glutamic acid, which comprises an amino acid that is absorbed in the body, and two other organic compounds.

In lab tests, the developers found the diclofenac was steadily released over 14 months, “far exceeding the duration noted in most previous reports, especially those from biodegradable matrices,” they note.

To evaluate the effectiveness of the method in preserving drug potency, the developers tested how well the diclofenac released from the thin film blocked the activity of an enzyme that is key to inflammation – cyclooxygenase of COX.

They note that the diclofenac remained active after release, producing “substantial COX inhibition at a similar level” to pills. This showed the method of attaching and releasing the drug had not damaged it.

Film-laden drug can be applied to injectable nanoparticles

The developers suggest the multilayered film can be applied onto biodegradable nanoparticles that are then injected directly into the part of the body that needs the medication. It can also be used to coat permanent devices, such as orthopedic implants, says the team.

The quantity of drug delivered can be adjusted by the number of layers of coating, they add.

They also believe their technique could also work for other drugs, for instance to treat conditions liketuberculosis where patients have to take medication on a regular basis for at least 6 months.

Other experts who read the paper say the thin-film technique has potential. Kathryn Uhrich, a professor in the Department of Chemistry and Chemical Biology at Rutgers University, describes it as “a really nice piece of work,” that she finds “really intriguing because it’s broadly applicable to a lot of systems.”

The team says they now need to work out the best way to bind different drug molecules to the thin-film, and then figure out how to optimize the technique for different bodily environments. They foresee a range of different tests, perhaps with drugs for both chronic pain and medication.

Prof. Hammond says the whole idea is to make life easier for people with chronic pain and inflammation.

The US Army and the US Air Force helped fund the study.

Medical News Today recently reported how a team from McGill University found deaths from prescription painkillers outnumber those caused by heroin and cocaine combined, citing that in 2010 in the US alone, prescribed painkillers were involved in over 16,000 deaths.

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