Peptide Drug Release Behavior from Biodegradable Temperature-Responsive Injectable Hydrogels Exhibiting Irreversible...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Biodegradable injectable polymers (IPs) are promising for sustained drug delivery.
• Glucagon-like peptide-1 (GLP-1) is a peptide drug requiring effective delivery methods.
• Temperature-responsive hydrogels offer controlled release capabilities.

Purpose of the Study:

• To investigate the release kinetics of GLP-1 from a novel biodegradable IP hydrogel.
• To compare GLP-1 release from irreversible (covalent gelation) and reversible (physical gelation) IP formulations.
• To evaluate the in vivo efficacy of the IP hydrogel for sustained GLP-1 delivery.

Main Methods:

• Synthesis of a temperature-responsive, biodegradable IP hydrogel utilizing a thiol-ene reaction for irreversible gelation.
• In vitro release studies of GLP-1 from both irreversible (F(P1/D+PA)) and reversible (F(P1)) IP formulations.
• Subcutaneous injection of the irreversible IP formulation into rats to assess in vivo GLP-1 pharmacokinetics.

Main Results:

• Sustained in vitro release of GLP-1 was observed from the irreversible IP formulation (F(P1/D+PA)) compared to the reversible formulation (F(P1)).
• Pharmaceutically active levels of GLP-1 were maintained in the blood of rats following subcutaneous administration of the irreversible IP formulation.
• The irreversible IP hydrogel demonstrated effective sustained release of the model peptide drug.

Conclusions:

• The developed biodegradable injectable polymer hydrogel, particularly the irreversible formulation, facilitates sustained release of GLP-1.
• This system shows potential for minimally invasive, long-term delivery of peptide drugs and other water-soluble bioactive agents.
• The covalent bond formation via thiol-ene reaction enables robust and controllable drug release profiles.