Get to the site of a problem, pack a big punch at the right time, and leave everywhere else alone. That’s what drugs of the future will have to do. Now, a Jello-like substance is giving patients a peek at that approach.
Researchers have created a gel that can attach to inflammation sites and slowly deliver drugs to combat a wide variety of ailments—ulcerative colitis, arthritis and mucositis, to name a few. Inflammation is part of the body’s immune response, bringing extra blood to an injured area, but in cases of chronic inflammation, the heat, pain, and swelling become a problem. Developed at the Laboratory for Accelerated Medical Innovation at the Brigham and Women’s Hospital, the hydrogel—a solid material with high water content—can carry a combination of drugs, and matches its drug release to the level of inflammation around it.
When the gel is injected into the joint of an arthritis patient, for example, it will only release its anti-inflammatory payload when the patient is experiencing a flare, a spike in pain and swelling. When it encounters healthy tissue, it stays intact and does not release its payload.
“There are lots of enzymes present in inflammation that can degrade the gel,” explains Jeff Karp, the principal investigator. That breakdown of the gel releases the drug it carries.
The gel could be used in radiation therapy for head and neck cancers, by working to soothe the painful mouth ulcers called mucositis that often develop from exposure to the high-energy radiation.
“Mucositis is the biggest complaint from patients, and it often leads to a lowered dose of the therapy,” says Karp.
If the side effects were alleviated, more patients might safely complete their scheduled course of therapy at the higher dose, and we would expect increased survival rates.
Not only is the drug delivery targeted, but the gel also attaches more easily to the site of inflammation than to the healthy tissues around it.
“Ulcers have more of a positive charge than the other tissues, so the materials we use are more negatively charged,” says Karp.
Targeted release reduces, to one-fifth or less, the extent to which the drug can be absorbed into whole-body systems, keeping the action at the local site where it is needed. Systemic absorption is often the origin of side effects. Doses can be spaced at longer intervals, and the drug is generally more effective and less toxic. For a patient with inflammatory bowel disease, this could mean replacing a daily enema to a once-per-week regimen that targets the positively-charged surface of an inflamed colon.
Inflammation-activated gels can be used to carry and release drugs other than anti-inflammatories. The latest application for Karp’s innovation is in limb transplantation. A hind limb from a black rat transplanted to a white rat is usually rejected around 11 days later. With regular immune suppressant therapy that time is extended to 33 days. But with an injection of hydrogel loaded with the same immune suppressant drug, the leg is maintained up to 150 days later. Working with the US Army, a group in Pittsburg is taking this research further, into the pig model. Pigs are often used to test such medical procedures, because their response closely mimics the human response.
Inflammation, though widespread in human ailments, is just one possible catalyst of drug release. In a future where a medical problem can activate its own solution, our diseases may all but order their drugs for delivery.
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