Taking a cue from hookworms—which are able to thrive in the gastrointestinal tract for up to two years—researchers at Johns Hopkins University created a fanged microdevice that sinks its teeth into mucus membranes and unleashes drugs gradually over time.
The parasite-inspired devices, which the researchers call "theragrippers," each come equipped with a drug-loaded polymer patch. The theragrippers are designed to change shape inside the body and latch onto the GI tract, which puts the tiny patches in place to release their drug payload, scientists at the school's Department of Chemical and Biomolecular Engineering said.
In a rat trial published in the journal Science Advances, the team showed the theragrippers could stick around in rodents' colons for a full day, leading to higher drug exposure over a longer period of time.
The theragrippers are built from metal thin films, armed with sharp "microtips" and capped with a heat-sensitive wax layer. Once they reach internal body temperature, the wax layer softens, causing the device to fold. The resultant force pushes the microtips into the mucus membranes, where the drug begins to release.
The device should work in any part of the GI tract, from the small intestine to the esophagus, the team figures, but it chose to focus on the colon in its animal trial. The team administered the devices rectally, because that route is preferred for pediatric patients and for localized therapies for diseases like ulcerative colitis.
In the trial, the team paired its grippers with the anti-inflammatory drug ketorolac, a decades-old pain med that clears quickly under normal circumstances, lingering in the body for less than three hours. It made for a “stringent” challenge to assess the microdevices' extended-release capabilities, the researchers said.
The team deployed thousands of grippers via a single shot into the rectum. Imaging showed the grippers remained inside the colon for at least 24 hours after administration. No short-term tissue damage or inflammation was noted, the team said.
The study showed that standard ketorolac’s plasma concentration dropped by 10 times within the first three hours after administration, whereas the theragripper-delivered drug saw a similar decrease in plasma concentration at hour eight. The theragripper drug also boasted sustained exposure between eight and 18 hours and an almost twofold increase in overall exposure compared with the standard drug.
Moving up the GI tract, the team showed its devices could attach to samples of pig stomachs and esophagi for more than 24 hours.
While the research is still in its early stages, the team hopes its theragrippers could overhaul drug delivery to the GI tract. It's a desirable target, thanks to the immense surface area of the intestine and the rich vascularization of mucus membranes along the entire GI tract, but the need for repeated oral or rectal administration of a drug can diminish patient adherence. Extended delivery via the microdevices could help, the team figures.
Mucoadhesive systems, like buccal patches, can extend a drug’s durability in the GI tract to five or six hours, but they’re unable to hang around much longer there. Mucus-penetrating particles provide another option, but the particles are typically washed out after a day as GI mucus clears the body.
Johns Hopkins University has filed patents related to the technology.