Tunable core water–shell alginate microparticles produced by microfluidics for sustained doxorubicin encapsulation and release

Core–shell particles have emerged as a promising platform for drug delivery due to their ability to spatially separate the drug-loaded core from the protective shell, enabling enhanced encapsulation efficiency, protection of sensitive therapeutics, and precise control over release kinetics. This study aimed to develop and optimize a droplet-based microfluidic approach for synthesizing water core–alginate shell particles. To mitigate the limitation of hydrophilic drug retention, these microparticles were designed to encapsulate the anticancer drug doxorubicin, enabling sustained release and reducing adverse side effects. Key parameters—including the flow rate of various phases, the junction width of the flow-focusing device, and the composition of alginate shell solution— were evaluated to achieve stable core–shell microgels with the desired morphology. By adjusting these parameters, monodisperse core-shell droplets (350 µm diameter, 43 µm shell thickness) were successfully tuned to slow drug release and increase resistance to immediate drug diffusion. To prolong the release duration, carboxymethyl cellulose particles and ε-poly-L-lysine were added to the core phase to form interpenetrating networks and electrostatic complexes at the water/alginate interface. This structural modification significantly enhanced drug encapsulation from approximately 67% to over 92%, while simultaneously prolonging the release duration beyond 120 hours under physiological conditions. Finally, the produced core-shell drug carriers were utilized for treating cancer cells, indicating a predictable and sustained cytotoxic effect against cancer cells. Overall, the proposed approach enables reproducible fabrication of tunable core–shell carriers with precise control over structural and functional parameters, offering promise for sustained chemotherapy delivery with reduced side effects.