Spatially programmable Janus particles from natural polymers for synergistic co-delivery of hydrophobic nutraceuticals

Abstract

The development of food-grade Janus particles for synergistic co-delivery of hydrophobic nutraceuticals remains a formidable challenge due to limitations in scalable fabrication and mechanistic understanding. Here, we propose a spatially programmable strategy that utilizes microfluidic control of the phase separation process to direct the assembly of natural polymers (zein and shellac) to construct anisotropic Janus particles and co-deliver hydrophobic nutraceuticals, thereby enabling continuous production and precise control. Functionalization with chitosan transforms the particles into superior Pickering emulsifiers, creating a robust gel-like network that dramatically enhances stability and modulates digestibility. Crucially, the anisotropic structure facilitated partitioned co-loading of curcumin and resveratrol, leading to synergistic effects including improved cellular uptake, potent cytotoxicity, and remarkable bioaccessibility. Molecular dynamics simulations elucidated the thermodynamic stability of Janus architecture and revealed the molecular mechanisms underlying partitioned loading. This integrated approach provides both a versatile platform for fabricating food-grade Janus particles and fundamental insights into their structure-function relationships, opening new avenues for engineered delivery systems in food and pharmaceutical applications.