Enhancing oral bioavailability and immunostimulatory activity of Glycyrrhiza uralensis polysaccharides through PLGA nanoparticle delivery system.

Glycyrrhiza uralensis polysaccharides (GUPS) are considered safe and effective natural medicine due to their extensive pharmacological activity and low toxicity. However, their large molecular weight (approximately 29 kDa) and high polarity restrict intestinal absorption, resulting in poor oral bioavailability. Here, GUPS-PLGA nanoparticles (GUPS-PLGA NPs, GPN) were prepared and their intestinal absorption characteristics and immunostimulatory activity were evaluated both in vitro and in vivo. Notably, GPN with a high encapsulation rate (63.18%) was prepared by response surface methodology. Furthermore, GPN exhibited a uniform spherical shape with a 242.4 ± 3.18 nm particle size, good stability, and sustained-release properties. Oral administration of GPN enhanced the intestinal retention of GUPS and improved its transport capacity in a Caco-2 cell monolayer model (0.66 vs. 1.36 Papp×10-6 cm/s). More importantly, GPN markedly promoted dendritic cell (DC) maturation through direct interactions and indirect effects across the Caco-2 cell monolayer. Furthermore, GPN significantly increased the number and activation state of T cells, DC, and macrophages in mice's spleen and mesenteric lymph nodes (MLN), demonstrating superior immune-enhancing effects. In summary, the PLGA-based oral drug delivery system markedly improved GUPS's intestinal absorption and efficacy, providing a theoretical foundation for developing GUPS as an oral medication and functional food.