Glucose-responsive insulin and diabetes
system discrete and small and yet at the same time be able to store at least one full day ’ s worth of insulin, the ability for mass industrial production and high biocompatibility – low toxicity levels. 10
In order to meet these criteria, a polymeric microneedle array with pyramidal needles was created, with a width of 400 μm and a height of 900 μm. A stress test was done on the needle array in order to determine the force required to fracture it which was found to be 0.90 ± 0.35 N per needle, which is sufficient for skin penetration. The needles are composed of an insulin-loaded glucose- responsive polymeric
matrix, meaning that the needles contain insulin and are responsive to glucose levels. These are prepared by creating a mixture of N- vinylpyrrolidone (NVP, the major monomer and solvent for other monomers),
Figure 3. Polymeric microneedles, insulin solution and formation of glucose-boronate complex. (Yu, et al., 2020)
Dimethylaminoethyl acrylate (DMAEA), 3-Aminophenylboronic acid (3APBA) and Ethylene glycol dimethacrylate (EGDMA), and by a photopolymerization done at 4 ° C, form the co-polymer p(NVP-co- DMAEA-co-3APBA) which is the aforementioned polymeric matrix. This is then purified by being placed in various chemical buffers, saline solutions, and mixtures to ensure the spread of the matrix is even and to remove any excess monomers which did not successfully polymerise, this is later shown by use of chromatography. This monomer mixture was chosen as phenylboronic acids can reversibly bind to a diol group found on a glucose molecule forming a glucose-boronate complex. 11 In order to stabilize this complex and increase the glucose recognition abilities at in vivo pH levels, the Lewis base DMAEA was used, which once protonated, stabilizes the negative charge on the boron atom, resulting in heightened glucose binding in hyperglycaemic conditions as it simply has more time to bind. If the sensitivity is not increased, due to the kinetics of the process, it would act the same during hyperglycaemic conditions as it would normoglycemic conditions, preventing proper
function. The glucose-boronate complex causes an increase in the negative charge of the matrix, which weakens the electrostatic interaction between the negatively charged insulin and polymers, causing the matrix to increase in volume under conditions of high glucose concentrations, allowing for insulin to be released from the microneedle. This was then tested in vivo on mice which had been given Streptozotocin (STZ), a drug which is toxic to insulin-producing
Figure 4. A graph to show insulin levels in the blood plasma of mice over time. Blue arrow shows point of patch administration (Yu, et al., 2020)
10 For this, and for much of the next paragraph, I am indebted to Yu et. Al. 2020. 11 Elsherif et al. 2018.
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