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Ultrasound-Triggered Hydrogel Shown to Deliver Cancer Drug

David Mooney

David Mooney (Harvard University)

24 June 2014. Bioengineers at Harvard University developed a technique with hydrogel and ultrasound that makes it possible to trigger short-term on-demand boosts of chemotherapy drugs. The team led by David Mooney of Harvard’s Wyss Institute for Biologically Inspired Engineering published its findings online today in the Proceedings of the National Academy of Sciences (paid subscription required).

Mooney and colleagues addressed a problem of delivering cancer drugs repeatedly on-demand to targeted regions in the body and in larger quantities for short bursts of time. Chemotherapy can be delivered today with injectable drug-releasing polymers to provide more targeted therapies, but in a constant flow over time. When hydrogel is the delivery medium, ultrasound delivered to the site can temporarily boost the quantity of drugs released, but the ultrasound destroys the hydrogel, making it a one-shot method.

The researchers in this study tested a type of hydrogel made with a natural polymer derived from algae and held together with calcium ions. With lab cultures, the team found a precise level of ultrasound breaks up the hydrogel bonds, making it possible to release its drug payload. But in an environment with more calcium, the hydrogel then recreates its chemical bonds, in effect healing the hydrogel and making it reusable as a drug-delivery mechanism.

In further lab culture tests, the tested this calcium technique for releasing mitoxantrone, a chemotherapy drug for treating breast and other types of solid and blood-related cancers. The test showed with this technique the hydrogel releases more mitoxantrone when submitted to a single burst of ultrasound, and subsequently reforms into its original state.

Mooney and colleagues then tested the technique on lab mice grafted with human breast cancer tumors. The researchers treated the mice with local injections of the hydrogel combined with mitoxantrone, which releases the drug in a constant flow over six months. With some of the mice, the team added a daily concentrated burst of ultrasound for 2.5 minutes that releases an extra shot of the cancer drug.

Not only did the researchers find the technique releases extra concentrated doses of cancer drugs in lab mice, but the extra drugs appear to affect the growth of cancer. The team reports the mice receiving the ultrasound and extra burst of drugs had less tumor growth than those receiving the hydrogel-drug injections alone. In addition, the mice receiving the ultrasound lived on average 80 days longer.

The researchers say the hydrogel/ultrasound technique could be used with drugs other than chemotherapy that require delivery of treatments at the right place and time, such as post-surgical pain medications and proteins for treating psoriasis and other auto-immune disorders.

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