Digestion-Derived Nanoparticles from Dairy and Plant-Based Milks: Comparative Analysis of Cellular Uptake Kinetics and Intestinal Barrier Interactions

The growing popularity of the plant-based milk alternatives highlights the need for a thorough evaluation of their colloidal properties, as variations in these properties may significantly influence their biological fate. This study compares the physicochemical characteristics, cellular interactions, and intestinal barrier effects of nanoparticles (NPs) derived from digested cow's milk and four commercial plant-based alternatives (almond, oat, soy, and coconut). Cow's milk NPs and plant-based NPs exhibited an average size ranging from 422 to 728 nm. The cellular uptake kinetics of these NPs demonstrated distinct patterns: rapid internalization for cow's milk NPs, delayed uptake for almond/oat NPs, transient retention for soy NPs, and rapid initial uptake followed by swift clearance for coconut NPs. Notably, all NPs (0.1-10% v/v) demonstrated excellent biocompatibility, with >95% Caco-2 cell viability and negligible inflammatory response in RAW264.7 macrophages; only coconut NPs induced reversible modulation of tight junctions (∼15% TEER reduction, ZO-1/claudin-1 downregulation). Functional analysis further identified soy and oat NPs as optimal candidates for sustained nutrient delivery, while cow's milk NPs favored rapid absorption. These insights aid in designing plant-based milks to tailor nutrient delivery profiles, safety and efficacy.