A Universal Co-Encapsulation Strategy for Hydrophilic and Hydrophobic Bioactives via Marangoni Effect-Driven Phase-Change Microcapsules

This study presents a novel food-grade Marangoni effect- and polyelectrolyte coacervate-based co-encapsulation strategy to simultaneously deliver hydrophilic and hydrophobic drugs, addressing the limitations of traditional systems in delivering active ingredients with diverse solubility. By encapsulating hydrophilic proanthocyanidins (PA) with chitosan/chondroitin sulfate polyelectrolyte complexes (Ch95/CS-PA) and co-loading them with hydrophobic vitamin D 3 (VD 3 ) in lauric acid phase change material (PCMs), composite microcapsules (PCMCs) were constructed using surface tension gradient-driven droplet self-splitting technology. Experimental results demonstrate that this method achieves efficient co-encapsulation through electrostatic interactions and low-temperature phase change solidification, with encapsulation efficiencies of 71.88% for PA and 82.49% for VD 3 . The dual-channel fluorescence tracing analysis via confocal laser scanning microscopy (CLSM) demonstrated that the Ch95/CS-PA achieved a uniform and stable distribution within PCM, with no ethanol-induced flocculation or Marangoni flow-driven drug leakage observed, thereby validating the efficacy of Ch95/CS as a hydrophilic drug delivery carrier. Thermal analysis (DSC, TGA) confirmed the stable phase change properties of the microcapsules (phase change enthalpy of 134.3 J/g), with no significant drug loss after 28 days of storage at 4°C. In vitro simulated gastrointestinal digestion showed that PCMCs remained intact in gastric fluid and released drugs in intestinal fluid through pH-responsive and bile salt-mediated micellization, enhancing the bioaccessibility of PA and VD 3 to 79.82% and 55.85%, respectively, compared to their free forms (control group: 41.16% and 16.21%). Compared to traditional multiple emulsion methods, this strategy reduces preparation time from hours to seconds and replaces mechanical energy input with chemical energy, offering a scalable solution for multi-component functional ingredient encapsulation in food and nutraceutical applications.