Microfluidic generation of single‑ and double‑core double emulsions for colon delivery

This study introduces a biocompatible microfluidic platform for generating water-in-water-in-oil (W/W/O) double emulsions tailored for colon-targeted drug delivery. Utilizing an aqueous two-phase system (ATPS) of polyethylene glycol (PEG) and dextran, PEG-in-dextran emulsions were formed in 3D-printed flow-focusing microdevices with different vertical confinements: a confined channel (0.4 mm height) producing stable two-core droplets and an unconfined channel (0.8 mm height) yielding single-core droplets. Hydroxyethyl cellulose (HEC) incorporation increased PEG core viscosity (from ∼1 to ∼361 mPa·s), ensuring stable droplet formation against the high-viscosity dextran shell (η₀ ≈ 3772 mPa·s). In the confined design, sensitivity analysis using random forest regression and SHapley Additive exPlanations (SHAP) showed oil flow rate predominantly controlled droplet size, while PEG flow rate governed core dimensions. Principal component analysis (PCA) combined with self-organizing map (SOM) clustering (validated via fuzzy c-means and K-means) categorized two-core structures into three regimes: large intersecting, small intersecting, and well-separated cores. Optimal single-core formation required PEG concentrations below 3.75 % w/v and dextran-to-PEG flow rate ratios ≤ 1. Crosslinked dextran–alginate capsules exhibited distinctive FTIR shifts indicating ionic interactions, an elastic modulus twice that of alginate-only gels, and preserved spherical morphology with central voids confirmed by SEM imaging. Encapsulation efficiency of 6 µm microplastics reached 96 % in the unconfined channel and 88 % in the confined channel, demonstrating the platform’s efficacy for colon-targeted particulate encapsulation. • A biocompatible microfluidic platform generates W/W/O double emulsions via a PEG–dextran aqueous two-phase system. • 3D-printed flow-focusing chips vary vertical confinement to control droplet shape, yielding single- or dual-core structures. • Random forest regression with SHAP analysis revealed oil and PEG flow rates as key factors influencing droplet and core sizes. • Crosslinked dextran–alginate capsules showed enhanced mechanical strength, validated by FTIR, SEM, and rheology. • Achieved up to 96 % encapsulation efficiency of microplastics, showing high potential for colon-targeted delivery.