Abstract
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. 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.
Highlights
The administration of drugs through the gastrointestinal (GI) tract offers improved compliance over injectables and better treatment outcomes [1]
While the oral route is the more preferred form of drug administration across all age groups, the rectal route is advantageous in the pediatric population as well as during medical emergencies, such as with unconscious patients [3, 4]
Mucus-penetrating particles (MPPs) have shown improved retention compared to mucoadhesive systems, in a mouse model, due to adherence to the mucus layer beneath the outer fast-clearing mucus [11, 12]
Summary
The administration of drugs through the gastrointestinal (GI) tract offers improved compliance over injectables and better treatment outcomes [1]. Mucus-penetrating particles (MPPs) have shown improved retention compared to mucoadhesive systems, in a mouse model, due to adherence to the mucus layer beneath the outer fast-clearing mucus [11, 12] These particles are removed after a day due to clearance of the underlying mucus layer, and it is unclear at this point if these MPPs can be made resident for longer times. Ring- or star-shaped devices, which are larger than the pylorus opening, can be retained in the stomach for several days before degrading into smaller pieces, which can pass through the pylorus [8, 17] Because these devices are larger than the pylorus opening, which is approximately 2 cm in diameter in adults, the potential risk of gastric obstruction for these devices needs to be evaluated. The highly acidic gastric fluids in the stomach can react with several drugs delivered by stomach-resident devices, rendering them ineffective
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