To contact or not: an investigation into the polymeric surface interactions with human insulin and their therapeutic implications

TL;DR

This study investigates how insulin interacts with polymer surfaces, leading to clumping that may reduce its effectiveness in treating diabetes.

Contribution

The novel use of FITC-labeled insulin and fluorescence lifetime measurements to map pH changes in insulin agglomerates.

Findings

Amine-terminated polymers caused larger insulin agglomerates with significant pH fluctuations.

Acid-terminated polymers showed less pronounced effects on insulin structure and pH.

Polymer interactions may reduce insulin bioactivity and glycemic control.

Abstract

Insulin, a therapeutic peptide used to treat Type I diabetes, interacts with polymers commonly found in healthcare settings via various hydrophobic interactions, which can trigger insulin agglomeration, thereby reducing its bioavailability and therapeutic efficacy. In this study, a fluorescein isothiocyanate (FITC)-labeled human insulin (λex = 490 nm; λem = 498–530 nm) suspension (0.125 mg mL−1, 0.25 mg mL−1, and 0.5 mg mL−1) prepared at pH 3 was interacted with fluorescent amine- (λex = 560 nm; λem = 570–650 nm) and acid-terminated (λex = 625 nm; λem = 640–720 nm) polystyrene particles (1 µm) at 37 °C for t = 2 h, 4 h, 24 h, 48 h, and 72 h. The variable fluorescence lifetime of FITC, driven by pH fluctuations, was used as a molecular pH meter to map pH alterations within insulin agglomerates. Larger agglomerates, with higher lifetime variations, were noticed for the amine-terminated particles, especially at longer timepoints, whereas such fluctuations were relatively subtle in the acid-terminated ones. Regions with lifetime variation spread beyond the adsorbed insulin layer on particles and merged with the peripheral zones of lower lifetimes inside the agglomerates. The results suggest that polymeric surfaces alter insulin's biochemical properties, with probable implications of reduced bioactivity, poor glycemic control, and (potential) additional side effects.

Insulin, a therapeutic peptide for Type I diabetes, can interact with polymers commonly found in healthcare settings via hydrophobic interactions, potentially triggering agglomeration while reducing its bioavailability and therapeutic efficacy.

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