Researchers at Brigham and Women’s Hospital, MIT and Novo Nordisk previously reported in Science on an orally-dosed device, the SOMA capsule, that delivers solid formulations of macromolecule drugs to the stomach. However, it has two key limitations: it can’t deliver drugs that have large dosage requirements, such as adalimumab, or drugs that require fast action, such as mealtime insulin and epinephrine.
Now, Giovanni Traverso, MD, PhD, MBBCH, a gastroenterologist in the Division of Gastroenterology, Hepatology and Endoscopy at the Brigham and MIT, and colleagues have created a version of the capsule that injects liquid formulations of pharmaceuticals into the gastric submucosa. Called L-SOMA, it’s described in Nature Biotechnology.
Mimicking the geometry of a self-righting tortoise, L-SOMA has a weighted bottom and hollow shell that lets it reorient itself when it arrives in the stomach. This design ensures the injection mechanism will always face the tissue wall and deliver the drug into the tissue rather than the gastric cavity.
For drug delivery, the L-SOMA relies on a staged, sequence-controlled, multi-spring actuation system that injects a hypodermic needle below the gastric mucosa, then delivers 80 microliters of a liquid drug into the submucosal space. The actuation mechanism is located on the shell of the capsule, eliminating the need for gastric fluid to enter the device and be in contact with the drug before injection.
To reduce the risk of an exposed needle in the gastrointestinal tract during capsule passage, the needle is retracted into the device after injection.
Efficacy in Animal Model
The researchers used an endoscope to place L-SOMA capsules in the stomachs of 31 anesthetized swine. The devices were left to actuate independently and deliver a clinically relevant dose of adalimumab, insulin, epinephrine or a glucagon-like peptide-1 analog:
- 28 swine (90%) demonstrated systemic uptake; in the other cases, the device did not actuate properly or the drug was not taken up into the animal’s bloodstream
- The bioavailabilities of all tested compounds were on par with those of subcutaneous and intramuscular doses in swine used as positive controls
- As negative controls, other swine underwent endoscopic gavage with epinephrine or adalimumab (drug load equivalent to that of the L-SOMA) and negligible uptake was observed
Safety in Animal Model
After dosing, the swine were monitored for one week or used for histologic studies. All animals monitored maintained their normal behavior and eating patterns. In some animals, minor bleeding was observed by endoscopy immediately after drug injection, but it stopped within minutes. No blood was detected in stool.
No abnormalities were seen on histology samples taken from the injection site within two hours. In three animals dosed on multiple occasions over three days, no abnormalities were noted on samples from the cardia, fundus or pyloric region.
Translation to the Clinic
Novo Nordisk partly funded this study and plans to study longer dosing regimens in preclinical models, then humans, with the characterization of any injection site reactions and other adverse events. Human investigations will include individuals varying in age, weight, height, diet and disease status.