Thermoplastic Molding of Silk-Curcumin Composites to Enhance Biological Properties

Silk fibroin protein is a natural protein biopolymer generated from the cocoons of <i>Bombyx mori</i> silkworms and a useful biomaterial for many different tissue engineering applications. Flexible process engineering, versatile chemistry, and aqueous processing allow morphological and structural modifications that tailor the physical, chemical, biological, and mechanical properties of this biomaterial. However, conventional solution-based processing methods can impose limitations in terms of solubility, stability as well as scalability. Recently, we reported a thermal processing technique to fabricate dense, regenerated silk fibroin-based structures (plastics) using solid-state thermoplastic molding to address these limitations. The present work expands the utilization of thermoplastic molding of silk-fibroin to enhance the biological properties of plant-derived compounds like curcumin, the active compound of turmeric (<i>Curcuma longa</i>). Curcumin is widely used in traditional medicines. The objective of this study was to study the feasibility of fabricating silk-curcumin composite thermoplastics with enhanced biological properties. The hypothesis was that protective silk thermoplastic formation after curcumin incorporation would enhance the biological properties of curcumin, via the protective features of silk combined with the sustained slow release of the compound to reduce toxicity without affecting anti-bacterial properties. The results show that significantly higher levels of curcumin (~25-fold) can be incorporated into thermoplastic molded silk compared with solution formulations, attributed to the hydrophobic nature and low solubility of curcumin in solution-based processing. The fabricated curcumin incorporated thermoplastics show excellent stability in harsh acidic conditions (e.g., gut-like environment) and low curcumin (~ 3% over 14 days) release. The protective silk–curcumin formation led to enhanced cytocompatibility of the curcumin with immortalized human colorectal adenocarcinoma (Caco 2) cells even at higher doses when compared to curcumin without silk. The intestinal epithelial barrier integrity based on zonula occluden 1 (ZO-1) assessments indicated that higher doses of curcumin in the thermoplastic molded silk did not result in detrimental effects to the intestinal barrier. Further work is ongoing to assess additional biological outcomes as well as potential areas of utility for these systems.