A sustained zero-order release carrier for long-acting, peakless basal insulin therapy

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Endocrinology

Background:

• Basal insulin therapy is crucial for diabetes management, aiming to replicate steady physiologic insulin secretion.
• Existing therapies often struggle to provide a consistent, peak-free insulin supply.
• Developing advanced drug carriers is essential for improving diabetes treatment efficacy.

Purpose of the Study:

• To design and evaluate a novel drug carrier for sustained basal insulin delivery.
• To mimic natural basal insulin secretion with a peak-free, prolonged, and steady release profile.
• To assess the in vitro and in vivo performance of the developed insulin delivery system.

Main Methods:

• PEGylation of insulin followed by incorporation into layer-by-layer assembled films with tannic acid (TA).
• Utilizing reversible hydrogen bonds between PEG-insulin and TA for gradual film disintegration and drug release.
• Conducting in vitro release tests to determine release kinetics (zero-order).
• Performing in vivo studies in streptozotocin-induced diabetic rats to evaluate plasma drug levels and blood glucose control.

Main Results:

• The developed films demonstrated a gradual release of PEG-insulin, following zero-order kinetics both in vitro and theoretically.
• Subcutaneous implantation in diabetic rats successfully maintained steady plasma drug levels and near-normal fasting blood glucose levels.
• A 50-bilayer film provided normoglycemia for approximately 16 days.
• The system successfully avoided initial burst release, a common issue in other drug delivery systems.

Conclusions:

• The novel PEG-insulin/TA layer-by-layer films offer a promising approach for sustained basal insulin delivery.
• The drug carrier effectively mimics physiologic insulin release, providing prolonged glycemic control.
• The film's thickness can be adjusted to control the duration of action, offering a customizable diabetes management solution.