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Nano-bio interactions are size-dependent. The present study investigates whether core–shell chitosan-alginate particle size governs biological activities as well as protein release profile. A coaxial electrospraying was used to fabricate bovine serum albumin (BSA)-loaded core–shell micro/nanoparticles and were fully characterized. The bio/hemocompatibility of the particles was assessed using MTT and hemolytic assays, respectively, followed by the uptake assessment using flow cytometry. Finally, protein absorption was investigated using SDS-PAGE. The SEM size of the microparticles, the hydrodynamic, and the actual sizes of the nanoparticles were 1.2 μm, 90.49 nm, and 50 nm, respectively. Interactions among two polymers and BSA were observed using DSC analysis. BET analysis showed a more surface area for nanoparticles. A sustained release trend of BSA was observed after 14- and 10-day for …