Process Optimization and Controlled Fabrication of Fish Oil Alginate Microbeads via Bipolar Wave Drop-on-Demand Electrospray: Enhancing Stability and Palatability

Fish oil is a rich source of omega-3 polyunsaturated fatty acids (PUFAs); however, its susceptibility to oxidation and poor palatability limit its practical applications. In this study, a bipolar wave-driven drop-on-demand (DOD) electrospray technique, assisted by a pulse generator, was employed to microencapsulate fish oil into size-controlled alginate microbeads. Response surface methodology (RSM) was employed to optimize process parameters, ensuring stable and scalable production. The optimized microbeads were characterized by SEM, FTIR, water uptake, in vitro release, stability studies, DPPH antioxidant assay, and MTT cytotoxicity assay, along with a human sensory evaluation for taste masking efficiency. The optimized conditions produced near-spherical microbeads with a mean diameter of 802 ± 9.00 µm, loading capacity (LC) of 15 ± 0.8%, and high encapsulation efficiency (EE) (99.25 ± 0.06%) at a flow rate of 0.052 mL/min, frequency of 3 Hz, duty cycle of 50%, and alginate-to-fish oil ratio of 10:1.7. The microbeads exhibited maximum water uptake at 4.5 h and achieved near-complete release within 6 h. Accelerated stability studies demonstrated limited shrinkage (1.3%) and a reduction in LC (4.0 ± 0.6%), along with enhanced antioxidant retention in encapsulated fish oil (88.5%) compared to free oil (50%) over six months. Cytotoxicity assessment using 3T3 fibroblast cells confirmed high biocompatibility, with cell viability exceeding 93% at concentrations ≤ 1.875 mg/mL. Palatability evaluation demonstrated significant improvements in taste, odor, texture, and overall acceptability compared with pure fish oil. Overall, the bipolar wave DOD electrospray approach provides a robust platform for controlled microbead production, enabling predictable size and production rate, while enhancing stability, controlled release, biocompatibility, and palatability of encapsulated fish oil.