Electrooxidation of Phenol on Polyelectrolyte Modified Carbon Electrodes for Use in Insulin Pump Infusion Sets

Abstract

Background: Many type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII) suffer from the phenomenon of unexplained hypoglycemia or "site loss." Site loss is hypothesized to be caused by toxic excipients, for example, phenolic compounds within insulin formulations that are used as preservatives and stabilizers. Here, we develop a bioinspired polyelectrolyte-modified carbon electrode for effective electrooxidative removal of phenol from insulin and eventual incorporations into an infusion set of a CSII device.

Methods: We modified a carbon screen printed electrode (SPE) with poly-L-lysine (PLL) to avoid passivation due to polyphenol deposition while still removing phenolic compounds from insulin injections. We characterized these electrodes using scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) and compared their data with data from bare SPEs. Furthermore, we performed electrochemical measurements to determine the extent of passivation, and high-performance liquid chromatography (HPLC) measurements to confirm both the removal of phenol and the integrity of insulin after phenol removal.

Results: Voltammetry measurements show that electrode passivation due to polyphenol deposition is reduced by a factor of 2X. HPLC measurements confirm a 10x greater removal of phenol by our modified electrodes relative to bare electrodes.

Conclusion: Using bioinspired polyelectrolytes to modify a carbon electrode surface aids in the electrooxidation of phenolic compounds from insulin and is a step toward integration within an infusion set for mitigating site loss.

Keywords: electrooxidation; infusion set; insulin pump; passivation; phenol; phenolic compound.

Figure 1.

Preparation and characterization of PDA-PLL-Cu coated electrodes. (a) Schematic illustration of coating PDA, PLL and Cu²⁺ on SPE. (b) Scanning electron microscopy (SEM) image of PDA coated SPE (left) and PDA-PLL coated SPE (right) scale bar: 200 nm. (c) Nyquist plots of bare SPE, PDA coated SPE and PDA-PLL coated SPE in 1X phosphate buffer saline (PBS) solution. Abbreviations: PDA, polydopamine; PLL, poly-L-lysine; SPE, screen printed electrode.

Figure 2.

Cyclic voltammetry (CV) measurement and peak current change of 3 mg/mL phenol or m-cresol in 1X pH 7.4 phosphate buffer saline (PBS) and 20 mg/mL glycerol on screen printed electrodes (a, b) without or (c, d) with stirring. The oxidization current intensity reduces significantly on the bare SPE, while on the PDA-PLL-Cu SPE the current decrease is alleviated, which indicates that polyphenol passivation is highly reduced on the modified SPE. Abbreviations: PDA, polydopamine; PLL, poly-L-lysine; SPE, screen printed electrode.

Figure 3.

Cyclic voltammetry (CV) measurement of 3 mg/mL phenol or m-cresol in 1X pH 7.4 phosphate buffer saline (PBS) and 20 mg/mL glycerol before and after rinsing with water, and the oxidation peak current of first scan before and after rinsing with water several times. The signal mostly recovers for the PDA-PLL-Cu modified electrode, while the bare SPE and PDA coated SPE showed no recovery of oxidization current, which suggests that the current decrease for the PDA-PLL-Cu SPE is mainly due to diffusion limitation, while the decrease for the bare SPE is due to passivation. Abbreviations: PDA, polydopamine; PLL, poly-L-lysine; SPE, screen printed electrode.

Figure 4.

Chronoamperometry (CA) measurement of 3 mg/mL phenol or m-cresol in 1X pH 7.4 phosphate buffer saline (PBS) and 20 mg/mL glycerol on screen printed electrodes. Current decay is reduced on the modified electrode which indicates that the passivation is alleviated. Abbreviations: PDA, polydopamine; PLL, poly-L-lysine; SPE, screen printed electrode.

Figure 5.

High-performance liquid chromatography (HPLC) results showing phenol concentration changes after 1 hour of electrooxidation. The table shows both the phenol reduction calculated from the chronoamperometry (CA) current and the exact phenol reduction measured via HPLC. On the PDA-PLL-Cu modified electrode, the concentration of phenol was reduced by 32%, while on the bare electrode the phenol concentration only reduced by 2% after oxidation removal. Abbreviations: PDA, polydopamine; PLL, poly-L-lysine; SPE, screen printed electrode.

Figure 6.

High-performance liquid chromatography (HPLC) results for insulin samples. Control is the insulin directly injected from human insulin injection without electrooxidation treatment. Insulin-exp is the insulin collected from flow cell after electrooxidation treatment. The intensity and integral area of insulin peak didn’t change between insulin collected from flow cell after electrooxidation and untreated insulin injection, indicating the insulin remained integrate in the solution after electrooxidation of phenols.