Glucose-responsive insulin and diabetes
pancreatic cells within mammals. Mice were chosen for this test, as they have very similar organs as well as bodily functions. These diabetic mice were split into two groups, one group to be given the glucose-responsive microneedle (GR-MN) patch and another group given non-responsive microneedle patch. Over time it was observed that both groups of mice, placed in a state of hyperglycaemia, normalized their blood sugar levels. However, normoglycaemia was only regulated in the group with the GR-MN patch, after 4 hours the group with the non-responsive patch returned to hyperglycaemia whereas the group with the GR-MN patch maintained normoglycaemia for more than 10 hours. Insulin levels in the blood plasma were measured at intervals with the use of an ELISA test which shows constant insulin levels in the blood plasma for the GR-MN patch compared to a large peak followed by near zero levels for the non-responsive patch and results from a subcutaneous insulin injection. 12
This same test was then done on minipigs, as their skin is a good model for human skin with its structure, thickness, lipid composition, hair spacing and various other reasons. The pigs were split into two groups each with either the GR-MN or the non-responsive patch, however, their blood sugar levels were constantly under monitor by use of a CGM system. Blood glucose levels in both groups decreased to normoglyceamia initially after 2 hours. The pigs were fed in the afternoon, and blood sugar levels in the pigs with the non-resonsive patch increased to a hyperglycaemic state, whereas in the pigs with the GR-MN patch, there was a slight increase which shortly was reduced back to normoglycaemia, and these levels were maintained until the next morning. Further testing showed that consecutive uses of the GR-MN patch allowed for controlled blood sugar levels for 48 hours in both diabetic mice and minipigs, and the GR-MN patch is able to maintain normoglycaemia in minipigs under normal feeding conditions for over 20 hours. 13
Minipigs treated with GR-MN patch
Minipigs treated with non-responsive patch
Figure 5. Graphs to show plasma glucose levels (PGL) in minipigs. Blue arrows to show time of patch administration, pink arrows to show feeding times. (Yu, et al., 2020)
This study is an overall success in the steps towards creating a method to help alleviate the dangers of those
suffering with type 1 diabetes and possible even help those with type 2. The process of fabricating the microneedle array can all be done very easily and in situ , making it easily mass-produced. Furthermore, the photopolymerization process is done using UV light in a vacuum at 4°C, and this low temperature prevents denaturing and ensures that the chemicals and the insulin used maintain their full bioactivity, as at higher temperatures they are likely to become less stable. The in vivo studies confirmed that the bioactivity of the insulin within the patches could be maintained at room temperature for over 8 weeks. 14 As for the problem of biocompatibility, the needle array is non-degradable and therefore will
12 Yu et al. 2020. 13 Ibid. 14 Ibid.
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