24 Matching Annotations
  1. Mar 2021
    1. Still, the SOMA represents a platform with the potential to deliver a broad range of biologic drugs, including but not limited to other protein- and nucleic acid–based therapies. The drug delivery efficacy achieved with this technology suggests that this method could supplant subcutaneous injections for insulin and justifies further evaluation for other biomacromolecules.

      This device could not only be used for pharmaceutical drugs, but since the enzyme activity was unaltered after compression, that suggests that protein-based and nucleic acid-based therapies, such as gene silencing, could be performed by this device. If further testing suggests that there are no long term effects, SOMAs could potentially replace the current insulin delivery methods, improving diabetic patients' quality of life.

    2. The discovery and purification of insulin transformed our capacity to effectively treat diabetes mellitus (3)

      This study showed that purification, or removal of other chemicals in the insulin solution, and treatment of insulin dependent diabetes mellitus (IDDM), or a disease often called sugar diabetes because the condition makes it difficult to convert food to energy. This leads to high sugar levels in the blood with intensive treatment (either multiple insulin injections per day or an external insulin pump) delayed the onset and slowed the progression of diabetic retinopathy (a disease of the eye caused by diabetes) when compared to conventional therapy.

    3. For example, milliposts fabricated with lysozyme and glucose-6-phosphate dehydrogenase demonstrated full enzymatic activity after undergoing the high-pressure manufacturing process (fig. S13).

      This is very important for using other medicines in the future. Other enzymes and medications such as lysozyme and glucose-6-dehygrogenase, worked in the fabricated milliposts. If the medicine you are treating a patient with requires a large dose, this SOMA may not be a good option because it can only hold so much medicine in the given space. It is also important to make the millipost stable enough to push through the gastric tissue.

    4. Additionally, to ensure safety in the case of a millipost misfire or device retention, we dosed six SOMA prototypes with 3-mm-long protruding 32-gauge stainless steel needles at once in swine; in this experiment, we performed x-rays over the course of 9 days and found no evidence of GI obstruction, pneumoperitoneum, or other adverse clinical effects

      In the case that the millipost did not dissolve, the authors used SOMAs with stainless steel needles to test that problem. They concluded that the SOMAs with needles that did not dissolve did not cause blockages in the GI tract, nor pneumoperitoneum, or the presence of air or gas in the abdomen. This means that the SOMAs do not cause GI blockages, or behavioral changes or other adverse effects in the swine model. This is promising news and could mean that the SOMAs would work in a human model.

    5. As tested, the SOMA functioned in vivo only in the fasted state. Animals with food and liquid in their stomachs showed no API uptake when tested with two different SOMAs, but three devices tested in empty stomachs demonstrated successful API delivery

      The SOMAs initially only worked when the stomach was empty, or the fasted state. When the SOMAs were dropped into the stomach where there was food, it would try to inject the insulin, but it would not pierce the stomach wall. When there was water, it pierced the stomach wall, but there was no insulin in the bloodstream.

    6. Increasing the depth and width of millipost penetration will increase drug loading but may compromise the gastric mucosa and increase perforation risk.

      Making the millipost longer or wider could make this SOMA more dangerous. The gastric mucosa, or stomach tissue is only 16 mm thick, so making a longer needle could allow for more drug to be stored, but it could cause damage to the stomach and could even lead the stomach to become perforated, which can lead to a deadly infection.

    7. D. M. Bass, M. Prevo, D. S. Waxman, Drug Saf. 25, 1021–1033 (2002).

      This paper found that extended release devices, like the one described in this paper, add therapeutic and convenience benefits, without adding any risks.

    8. G. Domokos, P. L. Várkonyi, Proc. Biol. Sci. 275, 11–17 (2008).

      This paper gave the authors the idea for the Leopard Tortoise shell shape to design this pill.

    9. G. Traverso et al., J. Pharm. Sci. 104, 362–367 (2015).

      This paper showed the authors that microneedles increase bioavailability of a drug and can be safely excreted by the body as seen using a swine model.

    10. L. Bolondi et al., Gastroenterology 89, 752–759 (1985).

      This paper showed the authors that direct injection into the stomach lining leads to a more predictable delivery rate when compared to a small intestine injection.

    11. I. P. Vazharov, J. IMAB 18, 273–275 (2012).

      This source showed that there were few injuries after multiple upper endoscopies, which are much more invasive. This was another source that showed the authors that injecting insulin into the GI tract is a safe way to deliver insulin, since it is less invasive than an upper endoscopy.

    12. D. K. Podolsky, J. Gastroenterol. 32, 122–126 (1997).

      This source explains that the mucosal surface in the GI tract is quick healing, giving the authors a good place to inject insulin without causing damage to the GI tract.

    13. T. A. S. Aguirre et al., Adv. Drug Deliv. Rev. 106, 223–241 (2016).

      This source shows that the bioavailability for even the most advanced drugs when taken orally is usually only 1-2%, meaning that very little drug is actually usable by the body, when a pill is taken orally. This led to the authors designing a pill that directly administered insulin directly into the GI tract.

    14. E. Moroz, S. Matoori, J.-C. Leroux, Adv. Drug Deliv. Rev. 101, 108–121 (2016).

      This study was important to the authors to find proper coatings for successful treatments of diabetes via the GI tract.

    15. M. J. Calvert, R. J. McManus, N. Freemantle, Br. J. Gen. Pract. 57, 455–460 (2007).

      This study explained that optimized treatment for Type II diabetes is delayed by, on average, 7.7 years. This meant that people with Type II diabetes were not well monitored or treated.

    16. Diabetes Control and Complications Trial Research Group, N. Engl. J. Med. 329, 977–986 (1993).

      This paper found that intense regular treatments of diabetes led to a decreased rate of progression to diabetic retinopathy (a disease of the eye caused by diabetes).

    17. L. Fallowfield et al., Ann. Oncol. 17, 205–210 (2006).

      This source describes the preference of people taking injections or tablets. The authors of that paper found that people preferred tablets over injections. This led the authors of this paper to design a tablet to treat diabetes as an alternative to insulin injections.

    18. The SOMA provides a way to deliver insulin orally and could potentially be used to administer other APIs.

      Since the delivery is oral and automatic, this device could improve the quality of life for people with diabetes. Since it worked with insulin, this device could potentially be used to inject medicines other than insulin directly into the bloodstream. This idea opens up new treatment options for people with daily injection treatments.

  2. Feb 2021
    1. The size and material makeup of the SOMAs are similar to those of FDA-approved ingestible devices such as OROS capsules, ingestible temperature sensors, and capsule endoscopy systems, supporting likely comparable environmental assessments (24, 30, 31).

      The OROS osmotic (OSM) dosage form optimizes extended-release drug administration by controlling the rate of drug release for a predetermined time. OSM products include prescription medications for urology, Central Nervous System, and cardiovascular indications, as well as over-the-counter nasal/sinus congestion medications. This shows that the SOMA device is similar to previous devices, meaning it is a less risky device, because other products have been approved with similar materials.

    2. Further research will be required to determine chronic effects caused by daily gastric injections, foreign body response, and local therapeutic agent exposure.

      To ensure the safety of patients, further testing will be required. There is much more work to be done to ensure that this device is safe and does not cause any long term effects. It is possible that injecting the stomach lining repeatedly over time could have some unknown effects or there could be an immune response to this device in some people. Since the authors do not know the long term effects of this device, it will not be available on the market for some time.

    3. A week after dosing the SOMAs, we performed endoscopies and saw no signs of tissue damage or abnormalities from the stomach injections. Veterinary staff monitored the swine twice daily and saw no signs of distress or changes in feeding and stooling patterns after administration.

      The authors used a scope and looked at the G.I. tracts of the swine that were fed the SOMAs. There were no visible signs of damage from the SOMAs and there was no evidence that these devices were hurting the swine based off of their behavior, eating habits, and the regularity of the excretion of their feces.

    4. To aid in protecting the SOMA from gastric content, we developed a valved membrane insert (fig. S12). As tested in vitro, the valve prevented food particles and viscous liquids from clogging the actuation pathway while still allowing the millipost to pass through.

      The authors designed a membrane that would stop food and fluid from getting into the millipost chamber, keeping the insulin safe, but would allow the millipost to be pushed through the membrane when the spring was activated.https://imgur.com/ncl6OiG

    5. Of note, the deliverable dose is constrained by the volume, formulation, and stability of the millipost.

      This is very important for using other medicines in the future. If the medicine you are treating a patient with requires a large dose, this SOMA may not be a good option because it can only hold so much medicine in the given space. It is also important to make the millipost stable enough to push through the gastric tissue.

    6. Integrity of the SOMA after GI transit was confirmed by examination of SOMAs recovered after excretion (see supplementary materials and methods).

      Here the authors gave 3 swine 3 SOMAs each and after the swine pooped them out, they examined them for visible damage. The authors said eight of the nine SOMAs were recovered and the ninth SOMA was accidentally disposed by accident during a cage cleaning. This showed that the SOMAs do not cause G.I. blockages, which means that they are safe to ingest.