Leveraging quantitative structure-activity relationships to design and optimize wall material formulations for antioxidant encapsulation via spray drying

• HPLC confirmed gallic acid retention up to 15.66 mg/mL in U+W+P+G formulation. • QSAR models achieved R² > 0.82, validating molecular descriptor predictions. • Whey, pectin & gum arabic synergize for enhanced encapsulation. • Hydrophilic & amphiphilic interactions boost wall material performance. • Optimized formulas yielded 12.34 mg/mL (polar) & 14.21 mg/mL (HBD-rich). This study addresses the critical challenge of optimizing antioxidant encapsulation to enhance stability and bioavailability during spray drying. To address this, the research integrates quantitative structure–activity relationship (QSAR) modeling with experimental validation to design wall material formulations rationally. In this work, we spray-dried grape juice using different wall materials. High-performance liquid chromatography (HPLC) confirmed that whey protein isolate, pectin, and gum arabic significantly influence encapsulation efficiency. QSAR models were developed using molecular descriptors such as topological polar surface area, molecular weight, and hydrogen bonding capacity, achieving high predictive accuracy (R² > 0.82). Whey protein favored polar antioxidants via hydrophilic interactions, gum arabic enhanced retention of hydrogen bond donor-rich antioxidants, and their combination demonstrated synergistic effects. The optimal formulation consisted of 2% whey protein isolate, 3% pectin, and 5% gum arabic, achieving encapsulation efficiencies of up to 14.21 mg/mL for hydrogen bond donor-rich antioxidants and 12.34 mg/mL for polar antioxidants. These results highlight the potential to tailor encapsulation systems to antioxidant characteristics. This study provides a resource-efficient strategy combining predictive modeling and empirical approaches with broad applications in functional food, nutraceutical, and pharmaceutical development, where stability and bioavailability are critical.