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Hydrogels Deliver Cancer Drugs ‘On Demand’ in New Treatment Approach

Ultrasound disrupts drug-loaded, injectable gels

Current drug delivery systems used to administer chemotherapy to cancer patients typically release a constant dose of the drug over time — but a new study challenges this “slow and steady” approach and offers a new way to locally deliver the drugs “on demand,” according to a report in the Proceedings of the National Academy of Sciences.

Researchers at Harvard University loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug. Like many other injectable gels that have been used for drug delivery for decades, this one gradually releases a low level of the drug by diffusion over time. To temporarily increase doses of drug, scientists had previously applied ultrasound, but that approach was a one-shot deal as the ultrasound was used to destroy those gels.

The new gel is different.

The team used ultrasound to temporarily disrupt the gel, causing it to release short, high-dose bursts of the drug — akin to opening a floodgate. But when they stopped the ultrasound, the hydrogel self-healed. By closing back up, the gel was ready for the next “on demand” drug burst, providing a way to administer drugs with a greater level of control than was possible before.

The advance holds promising implications for improved cancer treatment and other therapies requiring drugs to be delivered at the right place and the right time — from post-surgery pain medications to protein-based drugs that require daily injections. The new approach requires an initial injection of the hydrogel, but it could be a less traumatic, minimally invasive, and more effective method of drug delivery overall, according to lead investigator Professor David J. Mooney.

The researchers carried out most of their work with a gel made of alginate — a natural algae-derived polysaccharide that is held together with calcium ions. In a series of laboratory tests, the team found that with the right level of ultrasound, the bonds break up and enable the gel to release its drug cargo — but as long as the gel is in the presence of more calcium, the bonds reform and the gels self-heal.

Once the researchers knew that the hydrogel would self-heal, they tested a drug that they suspected the gel would hold well — the chemotherapy agent mitoxantrone, which is often used to treat breast cancer. As expected, the ultrasound triggered the gel to release the drug. Just a single ultrasound dose was effective, and the gel reformed after it was disrupted, making multiple cycles possible.

Source: Harvard University; June 23, 2014.

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