Photopolymerized thermosensitive hydrogels for tailorable diffusion-controlled protein delivery

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Thermosensitive hydrogels offer tunable properties for controlled release applications.
• ABA triblock copolymers combining physical and chemical cross-linking provide versatile material platforms.
• Methacrylated poly(N-(2-hydroxypropyl)methacrylamide lactate)s (p(HPMAm-lac)) and poly(ethylene glycol) (PEG) form the basis of these novel hydrogels.

Purpose of the Study:

• To investigate the tailoring of degradation and protein release characteristics in photopolymerized thermosensitive hydrogels.
• To establish structure-property relationships for optimizing hydrogel performance in protein delivery.
• To demonstrate the protein-friendly nature of the developed hydrogel system.

Main Methods:

• Synthesis of ABA triblock copolymers with thermosensitive A-blocks (methacrylated p(HPMAm-lac)) and a PEG B-block.
• Preparation of hydrogels using a combination of physical cross-linking (thermoresponsiveness) and chemical cross-linking (photopolymerization).
• Characterization of hydrogel properties including mechanical strength, cross-linking density, mesh size, swelling, and degradation.
• In vitro assessment of model protein (lysozyme, BSA, IgG) release kinetics and evaluation of protein structural and functional integrity post-release.

Main Results:

• Hydrogel mechanical properties, cross-linking density, mesh size, swelling, and degradation were tunable by adjusting polymer concentration.
• Protein release rate was dependent on protein size and hydrogel molecular weight between cross-links, following Fickian diffusion.
• Quantitative release of encapsulated proteins was achieved.
• The secondary structure and enzymatic activity of lysozyme were fully preserved, indicating minimal protein denaturation.

Conclusions:

• Photopolymerized thermosensitive hydrogels based on ABA triblock copolymers offer tunable degradation and protein release profiles.
• The developed system demonstrates excellent control over protein release kinetics, governed by Fickian diffusion.
• The hydrogels exhibit a protein-friendly environment, ensuring the integrity and activity of encapsulated biomolecules, making them promising for drug delivery applications.