On-demand release of insulin using glucose-responsive chitosan-based three-compartment microspheres

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Endocrinology

Background:

• Injectable glucose-responsive insulin delivery systems aim for sustained insulin release over 24 hours.
• A key challenge remains achieving on-demand insulin release, dependent on the delivery vehicle's degradation rate.

Purpose of the Study:

• To fabricate chitosan-based three-compartment microspheres (TCMs) for on-demand insulin release.
• To investigate the pH-responsive degradation of chitosan and its correlation with insulin release kinetics.
• To evaluate the efficacy of TCMs in regulating blood glucose levels in a type 2 diabetes model.

Main Methods:

• Chitosan-based TCMs were fabricated using gas-shearing microfluidics.
• Gradient chitosan concentrations were employed to create distinct pH-responsive compartments.
• Insulin was encapsulated at varying concentrations within each compartment.
• In vitro studies assessed insulin release profiles and biocompatibility.
• In vivo efficacy was tested in chemically induced type 2 diabetes cell models.

Main Results:

• TCMs demonstrated controlled, on-demand insulin release triggered by glucose-induced pH changes.
• The number of insulin-releasing compartments increased with rising blood glucose levels.
• TCMs exhibited enhanced structural integrity and prolonged drug action compared to single-compartment microspheres.
• Excellent biocompatibility was confirmed through in vitro experiments.
• Long-term blood glucose regulation (20-35 hours) was achieved in type 2 diabetes models.

Conclusions:

• TCMs represent a novel approach for on-demand insulin delivery, utilizing a multi-compartment design for precise glucose responsiveness.
• The gradient pH response and variable insulin loading enable tailored glucose management.
• This innovative microsphere system holds significant potential for advancing insulin analogs and diabetes therapeutics.