Glucose-Responsive Peptide Coacervates with High Encapsulation Efficiency for Controlled Release of Insulin

Abstract

A new glucose-responsive insulin delivery system is fabricated using biomimetic peptide coacervates derived from the Humboldt squid (Dosidicus Gigas) beak. Both insulin and glucose oxidase are coencapsulated within coacervate microdroplets. The glucose oxidase quickly responds to increasing glucose levels to generate a local acidic environment, thereby rapidly triggering the dissociation of pH-sensitive coacervates to release the insulin cargo. The rate of insulin release is dependent on the glucose level, increases under hyperglycemic conditions, and decreases under normoglycemic conditions. This glucose responsiveness mimics pancreatic β-cell function by releasing insulin according to glucose levels.

Protein Encapsulation Using Complex Coacervates: What Nature Has to Teach Us

“…[45][46][47][48][49][50] Furthermore, the phase-separated nature of these materials allows for strong partitioning of proteins into the polymeric phase, allowing for the easy preparation formulations with a high encapsulation and/or loading of protein. [12,[51][52][53] These high levels of incorporation are mainly due to the electrostatics and entropic gains associated with phase separation, but also take advantage of differences in the overall polarity of the coacervate environment compared to pure water. [54][55][56][57] To the best of our knowledge, there are only a few instances of ELPs and PEG/dextran delivery systems reported in the literature.…”

“…Traditional methods of determining protein concentration include indirect measurements using dyebased colorimetric readouts, such as the Bradford, [51,52] BCA, [171] and Lowry assays, [171] titration methods such as enzyme-linked immunosorbent assays (ELISA), and direct quantification via UV/Vis [56] or fluorescence spectrophotometry. [11,53,68,172] However, the choice of assay depends on the relevant concentration of protein in your sample, the ability to use or prepare a fluorescently-tagged protein, and the compatibility of the assay with the polymer materials present in the coacervate itself.…”

Glucose‐Responsive Insulin and Delivery Systems: Innovation and Translation

“…However, these systems suffer from premature leakage of insulin in the absence of glucose, an issue that requires further optimization. [31] Compared with bulk hydrogels, microgels or polymeric vesicles generally exhibit an elevated response rate to an external stimulus because of their decreased size and increased specific surface area. [32] Wu et al fabricated a positively charged acid-disintegrable microgel with covalently immobilized GOx and CAT, in which insulin was encapsulated through electrostatic interactions.…”

Recent Advances in Complex Coacervation Design from Macromolecular Assemblies and Emerging Applications

“…Lim et al. [ 123 ] developed a glucose‐responsive insulin delivery system using a biomimetic peptide coacervate inspired from Humboldt squid beak protein. Insulin and glucose oxidase (GOx) are incorporated in coacervate microdroplets with nearly 100% encapsulation efficiency, which is stable at neutral to slightly alkaline pH.…”