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

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.

Assessment of the immunogenicity of mechanically induced interferon aggregates in a transgenic mouse model.

Pump delivery of human interferon alpha-2B (IFNα2b) has the potential for inducing immunogenic drug aggregates. We therefore evaluated the immunogenicity of mechanically induced IFNα2b aggregates to assess this risk. Transgenic human-IFNα2b (TG) and wild-type (WT) FVB/N mice (n = 8 and n = 9/group, respectively) were administered mechanically agitated drug [45 Hz for 6 h (LLA) or 24 h (HLA)], chemically modified drug [low pH (pH 4.0) or metal oxidized (OXD)] or unstressed drug (native). Mice received IFNα2b (50 µg; 100 µg/mL; s.c.) formulations on days 0, 7, 14, and 21. Drug-binding and neutralizing antibody titers were determined after 28 d. Aggregate concentrations were highest in OXD and HLA formulations but OXD had more dimers/trimers. Geometric mean titers were 1:131, 1:728, 1:1573, 1:871, and 1:10,240 for WT mice (n = 9) and 1:207, 1:587, 1:1810, 1:571, and 1:2,153 for TG mice (n = 8) for native, LLA, HLA, pH4, and OXD groups, respectively. Mechanical agitation of IFNα2b induced equivalent titers of immunoglobulin to that of metal oxidation, both capable of binding to or neutralizing the drug in WT and TG mice. Thus, by limiting metal contamination and by inclusion of a stabilizing agent to mitigate drug aggregation, the risk of anti-drug immunoglobulin may be reduced in a pump delivery scenario.