Integrated Bioprocessing and Nanoencapsulation of Brewer's Spent Grain Phenolic Compounds: A Sustainable Valorization Strategy.

Brewer's spent grain (BSG), the major by-product of the brewing industry, is an abundant lignocellulosic biomass rich in phenolic compounds, although their association with the cell wall matrix limits their recovery and functional application. This study aimed to enhance phenolic compound recovery from BSG by integrating solid-state fermentation (SSF) with Aspergillus oryzae and green extraction technologies and to stabilize the recovered compounds using nanostructured lipid carriers (NLCs). Fermentation was evaluated for up to 7 days. Fermented and unfermented BSG were subsequently subjected to pressurized liquid extraction (PLE) and microwave-assisted extraction (MAE) with ethanol at 50-150 °C. Phenolic recovery was assessed by reducing capacity, DPPH antioxidant activity, and targeted UHPLC-MS/MS profiling. A two-day SSF period was selected as optimal, increasing reducing capacity 5-fold and antioxidant activity 7-fold compared with unfermented BSG. PLE provided the most efficient extraction performance, particularly at 130-150 °C, while SSF further enhanced phenolic recovery, especially at intermediate extraction temperatures. Targeted analysis quantified 10 phenolic compounds and related compounds and revealed compound-specific responses to processing. Fermented BSG extracted by PLE at 150 °C showed the highest p-coumaric acid content (16.0 ± 0.07 µg/g BSG), whereas the maximum trans-ferulic acid content was reached after MAE at 130 °C (21.5 ± 0.09 µg/g BSG). Selected PLE extracts were successfully incorporated into carnauba wax-based NLCs, producing particles below 300 nm and encapsulation efficiencies of up to 35%. Bioprocessing integrated with green extraction substantially improved the recovery of bioactive compounds from BSG, while lipid-based encapsulation provided a promising strategy for their stabilization, supporting the sustainable valorization of this brewing by-product.