Research ArticleDrug Delivery

Temperature-responsive biometamaterials for gastrointestinal applications

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Science Translational Medicine  17 Apr 2019:
Vol. 11, Issue 488, eaau8581
DOI: 10.1126/scitranslmed.aau8581

Shape-shifting drug delivery

Stimuli-responsive biomaterials can be useful for engineering controlled drug delivery systems. Babaee et al. designed two orally administered devices to change shape in the presence of warm water. A flower-like device could deliver drug into the upper esophagus via degradable millineedles attached to the “petals” (arms) of the device and could revert to a capsule shape to pass into the stomach in the presence of warm water. A second, flexible macrostructure could deliver large doses of drugs over 2 weeks while residing in the stomach before endoscopically delivered warm water triggered device disassembly via its thermosensitive polymer linkers. Proof-of-concept experiments in pigs reveal the potential of these thermoresponsive drug delivery systems.

Abstract

We hypothesized that ingested warm fluids could act as triggers for biomedical devices. We investigated heat dissipation throughout the upper gastrointestinal (GI) tract by administering warm (55°C) water to pigs and identified two zones in which thermal actuation could be applied: esophageal (actuation through warm water ingestion) and extra-esophageal (protected from ingestion of warm liquids and actuatable by endoscopically administered warm fluids). Inspired by a blooming flower, we developed a capsule-sized esophageal system that deploys using elastomeric elements and then recovers its original shape in response to thermal triggering of shape-memory nitinol springs by ingestion of warm water. Degradable millineedles incorporated into the system could deliver model molecules to the esophagus. For the extra-esophageal compartment, we developed a highly flexible macrostructure (mechanical metamaterial) that deforms into a cylindrical shape to safely pass through the esophagus and deploys into a fenestrated spherical shape in the stomach, capable of residing safely in the gastric cavity for weeks. The macrostructure uses thermoresponsive elements that dissociate when triggered with the endoscopic application of warm (55°C) water, allowing safe passage of the components through the GI tract. Our gastric-resident platform acts as a gram-level long-lasting drug delivery dosage form, releasing small-molecule drugs for 2 weeks. We anticipate that temperature-triggered systems could usher the development of the next generation of stents, drug delivery, and sensing systems housed in the GI tract.

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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