Silk protein plastics for sustained and controlled drug release.

Recent advances in thermomechanical processing have enabled the solid-state molding of silk into dense, plastic-like biomaterials with tunable mechanical and degradation properties. In this study, we developed enzyme-embedded, drug-loaded silk reservoirs via thermoplastic molding and evaluated their in vitro drug release and degradation profiles. Reservoirs processed at varying temperatures (95 °C, 125 °C, 145 °C) exhibited temperature-dependent crystallinity, which directly influenced drug release rates and degradation timelines over a period of 70 days. Embedding proteolytic enzymes within the silk matrix provided an additional layer of control, enabling tunable sustained drug release. To demonstrate therapeutic relevance, we encapsulated doxorubicin, temozolomide, and L-asparaginase and evaluated their cytotoxicity against U87 glioblastoma cells. Encapsulated drugs retained bioactivity post-processing, outperforming thermally treated drugs without silk protection. These findings present, for the first time, that silk matrices stabilize both small-molecule and protein-based therapeutics under thermal stress. This work establishes a modular platform for long-acting drug delivery, combining structural tunability, enzymatic responsiveness, and thermal stability. The approach holds promise for localized treatment strategies in oncology and other applications requiring sustained release of labile compounds.