Structure-Property-Performance Engineering of Hydrogel Depots for Long-Acting Peptide Delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Pharmacology

Background:

• Subcutaneous peptide delivery often suffers from initial burst release and short duration.
• Existing methods limit depot lifespan and increase pharmacokinetic variability.
• Long-acting peptide formulations are crucial for improving therapeutic outcomes.

Purpose of the Study:

• To engineer a dynamic, injectable hydrogel depot for sustained subcutaneous peptide delivery.
• To establish a modular formulation framework for controlling release kinetics.
• To evaluate the in vivo performance of lipidated peptide delivery using semaglutide as a model.

Main Methods:

• Developed an injectable hydrogel depot with tunable mechanics.
• Integrated cargo complexation strategies (hydrophobic and multivalent ion interactions).
• Incorporated sacrificial antioxidant excipients for oxidative stabilization.
• Evaluated performance using rheology, in vitro release, and in vivo pharmacokinetic/pharmacodynamic studies in rodents.

Main Results:

• Optimized formulations sustained semaglutide exposure for over six weeks.
• Achieved a two-fold reduction in peak-to-trough exposure.
• Demonstrated improved glucose control, weight regulation, and pancreatic islet preservation.
• Showed comparable total bioavailability to daily dosing.

Conclusions:

• The engineered hydrogel depot technology enables sustained peptide delivery for extended periods.
• The modular formulation framework allows for tuning release kinetics and improving stability.
• Results suggest potential for quarterly dosing of peptides in humans, reducing administration frequency and improving patient compliance.