Engineering lipid nanoparticles for dual-polarity bioactive delivery: Cold homogenization as a strategy for functional foods

The co-delivery of bioactive compounds with contrasting polarities remains a major challenge in the design of lipid-based systems for functional foods. Here, we report a cold homogenization strategy enabling the simultaneous encapsulation of hydrophilic caffeine and lipophilic curcumin within solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) formulated with food-grade excipients. The developed systems exhibited mean particle sizes in the range of 650–800 nm with narrow size distributions (PDI ≤ 0.3), indicating good colloidal uniformity. Notably, encapsulation efficiencies exceeded 90% for both compounds, demonstrating the effectiveness of this approach in overcoming thermodynamic partitioning limitations typically associated with hydrophilic molecules in lipid matrices. Fourier-transform infrared spectroscopy confirmed the molecular incorporation of both bioactives, suggesting intermolecular interactions within the lipid structure. The nanoparticles showed high retention (>98% over 72 h) and sustained co-release profiles without burst effects, with distinct release behaviors depending on carrier structure (e.g., curcumin release of 43.6% from SLN vs. 17.7% from NLC). These results highlight the role of matrix architecture in modulating the release of dual-polarity compounds. Overall, this work demonstrates, for the first time to the best of our knowledge, that cold homogenization enables efficient and stable co-encapsulation of hydrophilic and lipophilic nutraceuticals in a single lipid system using GRAS-compliant materials. This approach provides a scalable and versatile platform for the development of multifunctional delivery systems, with direct relevance for the formulation of next-generation functional foods and beverages.