Theragrippers Engineered for Efficient Drug Delivery

0

Scientists at Johns Hopkins say they have designed tiny, star-shaped microdevices that can latch onto intestinal mucosa and release drugs into the body. They cite a parasitic worm that digs its teeth into its host’s intestines as its source of inspiration.

David Gracias, PhD, a professor in the Johns Hopkins University Whiting School of Engineering, and Johns Hopkins gastroenterologist Florin M. Selaru, MD, director of the Johns Hopkins Inflammatory Bowel Disease Center, led a team of researchers and biomedical engineers that designed and tested shape-changing microdevices that mimic the way the parasitic hookworm affixes itself to an organism’s intestines.

The team published results of an animal study, “Gastrointestinal-resident, shape-changing microdevices extend drug release in vivo” in Science Advances.

“Extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens. However, because of clearance by intrinsic GI motility, device gastroretention and extended drug release over a prolonged duration are very challenging,” write the investigators.

theragrippers
A theragripper is about the size of a speck of dust. This swab contains dozens of the tiny devices. [Johns Hopkins University]

“Here, we report that GI parasite–inspired active mechanochemical therapeutic grippers, or theragrippers, can reside within the GI tract of live animals for 24 hours by autonomously latching onto the mucosal tissue. We also observe a notable sixfold increase in the elimination half-life using theragripper-mediated delivery of a model analgesic ketorolac tromethamine.

“These results provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery.”

Made of metal and thin, shape-changing film and coated in a heat-sensitive paraffin wax, named “theragrippers,” each roughly the size of a dust speck, potentially can carry any drug and release it gradually into the body.

Gradual or extended release of a drug is a long-sought goal in medicine. Selaru explains that a problem with extended-release drugs is they often make their way entirely through the gastrointestinal tract before they’ve finished dispensing their medication.

“Normal constriction and relaxation of GI tract muscles make it impossible for extended-release drugs to stay in the intestine long enough for the patient to receive the full dose,” says Selaru, who has collaborated with Gracias for more than 10 years. “We’ve been working to solve this problem by designing these small drug carriers that can autonomously latch onto the intestinal mucosa and keep the drug load inside the GI tract for a desired duration of time.”

Thousands of theragrippers can be deployed in the GI tract. When the paraffin wax coating on the grippers reaches the temperature inside the body, the devices close autonomously and clamp onto the colonic wall. The closing action causes the tiny, six-pointed devices to dig into the mucosa and remain attached to the colon, where they are retained and release their medicine payloads gradually into the body.

open theragripper
When an open theragripper, left, is exposed to internal body temperatures, it closes on the intestinal wall. In the gripper’s center is a space for a small dose of a drug. [Johns Hopkins University]
Eventually, the theragrippers lose their hold on the tissue and are cleared from the intestine via normal gastrointestinal muscular function.

Gracias notes advances in the field of biomedical engineering in recent years.

“We have seen the introduction of dynamic, microfabricated smart devices that can be controlled by electrical or chemical signals,” he says. “But these grippers are so small that batteries, antennas, and other components will not fit on them.”

Theragrippers, continues Gracias, don’t rely on electricity, wireless signals, or external controls. “Instead, they operate like small, compressed springs with a temperature-triggered coating on the devices that releases the stored energy autonomously at body temperature.”

The Johns Hopkins researchers fabricated the devices with about 6,000 theragrippers per 3-inch silicon wafer. In their animal experiments, they loaded a pain-relieving drug onto the grippers. The researchers’ studies found that the animals into which theragrippers were administered had higher concentrates of the pain reliever in their bloodstreams than did the control group. The drug stayed in the test subjects’ systems for nearly 12 hours versus two hours in the control group.

This site uses Akismet to reduce spam. Learn how your comment data is processed.