Green-by-Design Biodegradable Elastomeric Implants for Solvent-Free, Long-Acting Protein Delivery

Introduction: Sustainable pharmaceutical manufacturing requires delivery technologies that reduce hazardous solvents, energy-intensive processing, and persistent material waste without compromising therapeutic performance. This study evaluates biodegradable poly(diol-co-tricarballylate) (PDT) elastomers as a green-by-design platform for localized, long-acting protein delivery. 

Methods: PDT elastomers were synthesized by mild polycondensation of tricarballylic acid and aliphatic diols, followed by acrylation and visible-light photocrosslinking. Interleukin-2 (IL-2) was incorporated in solid form without organic solvents. Release behavior, protein bioactivity, polymer degradation, and antitumor efficacy were evaluated, with release modulation achieved through crosslinking density, excipient composition, and implant geometry.

Results: The PDT matrices provided tunable, near-linear sustained IL-2 release through an osmotic-driven mechanism. IL-2 retained >90% bioactivity during the first month of release. Controlled elastomer degradation generated minimal acidic by-products, supporting biocompatibility while avoiding ultraviolet irradiation and solvent-based protein processing. In vivo, sustained subcutaneous IL-2 delivery prevented tumor growth in a murine Renca carcinoma model.

Conclusions: Visible-light-cured PDT elastomers integrate solvent-free protein loading, biodegradable materials, mild fabrication conditions, and long-acting therapeutic delivery within a single platform. These findings support PDT implants as a sustainable approach to advanced biologic formulation and controlled release.