Origami-Inspired Capsule Shows Promise for Multi-Day Dosing and Sustained Drug Release

By Dr. Chinta SidharthanReviewed by Laura ThomsonAug 11 2026

Missed or skipped medication doses account for a substantial share of preventable hospital costs each year. In a recent study published in Nature Communications, a Massachusetts Institute of Technology (MIT)-led team designed and built a folded, origami-inspired capsule that unfurls inside the stomach and steadily releases a drug for several days from just one swallow.

Benefits of Extended-Release Drugs Technologies

Missed or delayed doses reduce how well treatments work and measurably add to avoidable healthcare costs. Extended-release technologies address this by delivering a drug continuously from a single dose rather than through repeated administration, supporting better adherence.

For medicines taken orally, sustained release beyond a day or two is difficult, since the digestive tract moves ingested material through relatively quickly. Engineers have explored several strategies to prolong gastric residence, including devices that float on stomach fluid, swell after swallowing, adhere to the stomach lining, or physically change shape once inside the body.

Shape-changing systems tend to achieve the longest residence times and carry a reasonable proportion of drug by weight, but they are often built from multiple components, raising manufacturing complexity and limiting the drug types they can carry.

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The Study

In the present study, researchers at MIT and Brigham and Women's Hospital designed a dosage form based on a circular variant of the Miura-ori origami fold pattern, in which two tapered sections fuse into a three-dimensional, toroidal structure once deployed.

The device, which they call the origami-inspired dosage form (ODF), folds compactly enough to fit inside a standard size-000 ingestible capsule and expands when the capsule is dissolved, into a shape too large to pass through the pylorus.

The team used geometric modeling to identify the unit-cell dimensions, sheet thickness, and angles that maximized both the capsule space occupied by the folded device and its deployed diameter, while remaining compatible with typical human pylorus dimensions. The structure was fabricated from poly(ε-caprolactone), a biodegradable, Food and Drug Administration (FDA)-approved polymer. This polymer was mixed with the fluoroquinolone antibiotic moxifloxacin.

The mixture was melt-blended in a twin-screw micro-compounder, formed into thin sheets with a film applicator, and cut into the origami pattern with a laser cutter. The researchers also added pH-sensitive bands to the structure to dissolve in the intestine's near-neutral environment, which would promote safe breakdown once the device left the stomach.

The mechanical strength of different formulations was assessed through tensile testing before and after incubation in simulated gastric and intestinal fluids. Additionally, the release kinetics of the structure were also measured in vitro in simulated gastric fluid, and thermal and acid stabilities of moxifloxacin were confirmed using high-performance liquid chromatography.

The team evaluated the device in vivo in female Yorkshire swine. Drug-loaded and drug-free devices were delivered through nasogastric tubes and tracked with X-ray imaging. Some devices were also placed directly into the intestine to assess blockage risk. The serum drug concentrations were measured using blood samples, and a pharmacokinetic analysis was performed to compare the elimination of the drug between the device and an unformulated dose.

What Were the Key Findings of the Study?

The study found that the origami-inspired capsule remained lodged in the stomach for extended periods while releasing a steady stream of drug, substantially outperforming an unformulated dose of the same medication. In vitro testing showed the device released roughly 70% of its loaded moxifloxacin over five days at a near-constant rate.

In the animal models, all 20 devices that were administered remained in the stomach for at least one week, with some persisting for as long as three weeks, while the devices that were placed directly into the intestine broke apart and passed within a single day.

However, drug-loaded devices tended to leave the stomach somewhat sooner than drug-free controls, which the researchers attributed to material loss as the drug diffused out. None of the animals showed any evidence of gastrointestinal obstruction, vomiting, or altered feeding behavior. Furthermore, blood testing showed that animals receiving the sustained-release device maintained detectable moxifloxacin for up to four days, compared with roughly two days for an unformulated dose.

While the peak concentration was lower with the device, the serum levels stayed closer to that peak for longer, remaining at about 70% of the maximum on the first day rather than dropping to around 15% as was seen with immediate release. The drug's elimination rate constant was roughly 65% lower when delivered by the device.

The authors noted that the precise mechanism by which the structure broke apart could not be directly observed, as devices could not be retrieved after intestinal passage. However, in vitro observations indicated gradual softening rather than fracturing into sharp pieces. Another limitation was drug loading, which is currently capped below 400 milligrams per device. This limits its use to lower-dose medications, unless multiple devices are administered together.

Conclusion

The study demonstrated that a single-material, origami-folded capsule can remain in the stomach for up to three weeks and sustain drug release over several days in a large-animal model. The performance of this capsule also exceeded that of an unformulated dose.

The researchers believe that this platform could eventually support multi-day dosing of antibiotics, antiparasitics, or other chronic medications, particularly in settings where consistent access to healthcare is limited.