We also performed a laparotomy followed by a gastrostomy to manually place milliposts into the gastric tissue. These experiments yielded comparable pharmacokinetics and systemic uptake.
The authors made a surgical incision into the abdominal cavity and performed a surgical operation to make an opening in the stomach in order to manually implant the millliposts into a swine stomach. This shows the drug being taken in at a very similar rate as to when the device was ingested.
milliposts were inserted into the submucosa of swine stomach tissue after being ejected from a SOMA with a 5-N spring. The insulin tips reached the same depth as dye injected by a Carr-Locke needle (Fig. 3, D to F and H). To ensure a safety margin on the insertion force, we ejected stainless steel milliposts using 9-N steel springs (k = 1.13 N/mm) into ex vivo swine tissue, and these still did not perforate the tissue
The authors show that a force of 5 N from the spring allows the milliposts to enter into the tissue of the swine's stomach. They verify that this will be safe by testing a force of 9 N, which is larger than the used 5 N, showing that even a larger force will not cause the tissue to rip or be damaged.
Dissolution profiles in vitro demonstrated complete dissolution within 60 min
The authors tested in a simulation that the millipost will dissolve within 60 minutes after released, so that it is not staying in the body for too long of a time period after it is released.
Stability studies conducted at 40°C showed that the insulin milliposts remained stable in a desiccated environment for 16 weeks (fig. S6), as compared with 4 weeks of stability for a liquid formulation.
The authors show that the device can be stored for an extended period of time in a warm, dry environment, as well as a slightly shorter time in a liquid environment. This demonstrates that the device can be safely stored and it will not affect the device.
Raman spectroscopy validated the protein structure of the API after high-pressure exposure
The authors used a technique to determine vibrational modes of molecules to analyze the chemical structure of the API used after having it put under high pressure.
Compression tests measured a Young’s modulus of 730 ± 30 MPa, like that of PEO, and an ultimate strength of 20.0 ± 0.7 MPa, ensuring millipost integrity after external force
The authors tested how much pressure could be put on the milliposts, which gave the stiffness of the material to be 730+/- 30 MPa. The maximum pressure the material can withstand before breaking is 20 +/- 0.7 MPa. These numbers are used to make sure a pressure higher than that is not used, ensuring the milliposts will stay intact.
We compared these experiments to swine dosed with SOMAs designed to localize the milliposts to the stomach wall without inserting them into the tissue (n = 5). These swine experienced no insulin uptake or blood glucose–lowering effects
The authors tested the device being ingested, but without the milliposts being inserted into the stomach tissue. No insulin was released, demonstrating that insulin will not leak out of the device without it being implanted in the tissue.
Additionally, we showed the potential for sustained-release delivery by subcutaneously implanting milliposts loaded with 1 mg or greater of API. These milliposts released API with a near zero-order rate for at least 30 hours
The authors tested how the milliposts would perform with an increased amount of API loaded in it. The device showed that even with more API in it, the drug would be delivered at a constant rate and would continue to be administered for 30 hours.
Milliposts from these experiments released drug at a near zero-order kinetic rate
The release of the drug was shown to be near constant, independent of the concentration that was being released.
We administered milliposts loaded with 0.3 mg of human insulin to swine and measured blood glucose and API levels. Endoscopically dosed SOMAs localized to the stomach wall and self-oriented before injecting milliposts into the tissue. Histology confirmed that the SOMA delivered milliposts through the mucosa without injuring the outer muscular layer of the stomach
The authors test the device in a swine stomach. The device successfully found its way to the wall of the stomach and was able to stand itself up in the correct direction and insert the post into the tissue, without causing any damage.
simulations and in vitro experiments, we demonstrated that sucrose dissolution could be tuned to release a compressed spring at a predicted time with a precision of 11.4 s throughout a 4-min time period
The authors show that the spring has a high precision, so that the time that the spring will actually be released can be very accurately estimated.
Using a custom stage, we demonstrated that milliposts displaced in vivo swine tissue by 7 mm when we applied on the order of 1 N of force
The authors test the relationship between how much force is applied to the milliposts and how deep the post goes into the tissue of the swine.
Mechanical and chemical characterization studies on the milliposts supported insulin stability.
The authors tested the mechanical and chemical properties of the milliposts used to deliver the insulin. The tests concluded that the milliposts would be able to successfully delivery the insulin while keeping it stable.
COMSOL
A simulation software to create accurate models
GI fluid
Fluid that aids digestion
sucrose
A common sugar
isomalt
A sugar substitute
micro–computed tomography (micro-CT)
3D imaging technique using x-rays to see the inside of an object by viewing it slice by slice
Histology
The study of the microscopic structures of tissues