|The hydrogel ultrasound process--Courtesy of Harvard|
Harvard University researchers have developed a system for releasing high doses of drugs in short bursts using ultrasound and self-healing hydrogel. Future therapy could therefore be highly customized and locally delivered at specific times, as opposed to the dominant sustained release paradigm.
"We want to give clinicians the ability to deliver drugs as locally as possible combined with the flexibility to temporally control the dose," said Nathanial Huebsch, co-author of a paper describing the research in the Proceedings of the National Academy of Sciences, in a news release.
Key to the breakthrough was finding self-healing hydrogel--a hydrophilic polymer chain--enabling multiple rounds of treatment, and matching it with the optimal intensity of ultrasound and a drug that it holds well, the researchers said. They settled on hydrogel made from alginate, found in algae, and used it to release the chemotherapy drug mitoxantrone in a series of repeated bursts. The intensity of the ultrasound was lower than that required to destroy tumors.
Mice with implanted breast cancer tumors who received mitoxantrone using the ultrasound pulse delivery method survived 80 days longer than those who received the drug in a conventional manner.
"We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seems to be particularly effective in killing cancer cells," said Harvard scientist David Mooney.
According to Harvard bioengineering professor Don Ingber, "Dave's work shows that these new responsive hydrogels that remodel reversibly when exposed to ultrasound energy at the nanoscale not only provide a new way to administer drugs on demand, they also produce better responses to therapy even in a disease as difficult to treat as cancer."
The team believes the methodology could be used to deliver other substances such as proteins and DNA plasmids, and will explore the potential to independently release two separate drugs from the same hydrogel.