A Versatile Microfluidic Manufacturing Platform for Macroscale Multicore Hydrogel Capsules Toward Programmable Oral Delivery of Therapeutics

The rapid expansion of personalized precision medicine and the increasing prevalence of chronic diseases have rekindled crucial needs for individualized therapeutic drug delivery systems. Conventional oral formulations are largely based on standardized designs for mass production and therefore lack the flexibility required for patient-specific therapeutic strategies, including combination dosing and controlled release. We report a rapid microfluidic fabrication method for millimeter-scale hydrogel capsules (macrocapsules) as a versatile platform suitable for oral delivery of therapeutics. Our technique enables reliable production of uniform macrocapsules containing multiple aqueous cores physically isolated by oil layers within an alginate hydrogel shell. Independent control of flow rates and alginate formulation allows systematic tuning of capsule size, multicore organization, and cargo loading. These macrocapsules maintain structural integrity under physiologically relevant mechanical and chemical stress conditions mimicking gastric environments, effectively protecting sensitive cargos throughout the typical gastric residence time. Simple tuning of the alginate concentration can further modulate the release onset and profile in intestinal conditions in a precisely controlled manner. The platform can be easily extended to produce multicompartmental macrocapsules that accommodate multiple cargos with independent and programmable release without cross-interference. Combined, these results represent a significant step toward versatile and programmable oral therapeutic delivery systems.