Photocrosslinked anhydride systems for long-term protein release

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Regenerative Medicine

Background:

• Injectable delivery systems are crucial for localized therapeutic delivery, particularly in regenerative medicine.
• Polyanhydride (PA) networks offer potential as encapsulation matrices for sustained release of therapeutics.

Purpose of the Study:

• To investigate the potential of photocrosslinked polyanhydride networks for long-term encapsulation and release of macromolecules.
• To evaluate the in vitro release profiles and activity retention of model proteins from these PA networks.

Main Methods:

• Fabrication of photocrosslinked polyanhydride networks using sebacic acid dimethacrylate (MSA), 1,6-bis-carboxyphenoxyhexane dimethacrylate (MCPH), and poly(ethylene glycol) diacrylate (PEGDA), with calcium carbonate supplementation.
• Formulation of model proteins (horseradish peroxidase (HRP) and fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA)) using cyclodextrin excipient and gelatin-based wet granulation prior to incorporation.
• Quantification of protein release via activity assay (HRP) and fluorescence (FITC-BSA), with SDS-PAGE analysis for HRP visualization.

Main Results:

• Proteins were released from the PA networks with distinct release behaviors, achieving sustained release for up to 4 months.
• Protein activity was retained throughout the release period, demonstrating the system's biocompatibility.
• Hydrophobicity of the network influenced release rates, with more hydrophobic networks showing slower release.
• Poly(ethylene glycol) diacrylate (PEGDA) incorporation was essential for maintaining network integrity during degradation.

Conclusions:

• Photocrosslinked polyanhydride networks serve as effective matrices for the long-term, controlled release of macromolecules with retained activity.
• The developed injectable system demonstrates significant potential for localized, sustained therapeutic delivery in regenerative medicine applications.
• Tunable network properties allow for customization of release profiles based on therapeutic requirements.