pH-Responsive Colloidal Guar Gum Nanoparticles for Rosmarinic Acid Delivery: Role of the Degree of Carboxymethylation

The oral delivery of polyphenolic compounds such as rosmarinic acid (Ros) is limited by poor gastrointestinal stability and early release, resulting in low bioaccessibility. Herein, carboxymethylated guar gum (cmGG)-based nanoparticles were developed as a pH-responsive colloidal delivery system to enhance Ros stability, prevent early release, and improve intestinal bioaccessibility. In this context, pH-responsiveness refers to pH-dependent modulation of degradation, and stabilization along the gastrointestinal tract, rather than an abrupt pH-triggered burst release. Guar gum was chemically modified to different degrees of carboxymethylation to enhance its colloidal stability under gastrointestinal conditions, reduce polymer degradation, and enable a more controlled release of the phenolic compound Ros. Comparative evaluation of cmGG systems with varying degrees of carboxymethylation revealed that nanoparticles prepared from highly substituted cmGG exhibited superior colloidal stability and acid resistance, contributing to effective protection of Ros under gastric conditions. Ros-loaded guar gum nanoparticles effectively suppressed release at acidic pH while enabling controlled and sustained release at intestinal pH. Simulated gastrointestinal digestion studies demonstrated that Ros-loaded carboxymethylated guar gum nanoparticles significantly enhanced the gastrointestinal stability and bioaccessibility of Ros compared with non-carboxymethylated guar gum nanoparticles. Overall, these findings indicate that the degree of carboxymethylation is a critical design parameter for tuning colloidal behavior and release performance under the varying pH conditions encountered throughout the gastrointestinal tract in guar gum-based nanoparticle systems.