Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Traditional hydrogel depots face limitations like hydrolysis and low capacity.
• Current water-free systems often require surgical implantation, hindering clinical use.

Purpose of the Study:

• To develop a biodegradable, water-free, injectable protein delivery system.
• To overcome administration challenges associated with current depot systems.

Main Methods:

• Utilized inverse electron demand Diels-Alder reaction between norbornene- and tetrazine-functionalized PEG macromonomers.
• Modified precursors (methyl substitution, oxygen incorporation) to tune gelation and mechanical properties.
• Incorporated hydrolytically cleavable groups for biodegradability and tuned stability with phenyl carbamate/carbonate esters.

Main Results:

• Achieved rapid in situ gelation (<11 seconds) of precursor mixtures.
• Demonstrated tunable gelation times and cross-linking density via chemical modifications.
• Successfully achieved controlled release of glucose oxidase for 500 days.

Conclusions:

• Developed a promising water-free injectable system for protein delivery.
• The inverse electron demand Diels-Alder reaction offers a viable route for in situ hydrogel formation.
• The system shows potential for long-term, controlled drug delivery applications.