Preparation, characterization and immune enhancement study of <scp> <i>Hericium erinaceus</i> </scp> polysaccharide‐loaded polyethyleneimine‐modified poly(lactic‐ <i>co</i> ‐glycolic acid) nanoparticles

BACKGROUND: Hericium erinaceus polysaccharides (HEPs) exhibit remarkable immunomodulatory properties but are hampered by poor oral bioavailability. To overcome these limitations, this study developed and optimized HEP-loaded polyethyleneimine (PEI)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HEP-PPNPs) as a novel drug delivery system. RESULTS: Following formulation optimization, HEP-PPNPs were successfully prepared using a modified double-emulsion solvent evaporation method, achieving a high encapsulation efficiency of 71.78%. The prepared nanoparticles exhibited a spherical morphology with a mean particle size of 176.4 ± 3.6 nm, a narrow polydispersity index of 0.131 ± 0.005 and a positive zeta potential of +32.8 ± 0.3 mV. Biological assessments on RAW264.7 macrophages showed that HEP-PPNPs significantly enhanced phagocytic activity and promoted the secretion of key immunomodulatory cytokines (TNF-α, IL-6 and IL-4) without cytotoxicity at effective concentrations. Furthermore, HEP-PPNPs markedly upregulated the expression of co-stimulatory molecules CD80 and CD86. The immunoenhancement effect of HEP-PPNPs was significantly superior to that of both free HEPs and unmodified HEP-PLGA nanoparticles. CONCLUSION: The developed HEP-PPNPs system effectively mitigates the pharmacokinetic limitations of native HEPs. The formulation demonstrates favorable physicochemical properties and elicits a stronger immunostimulatory response compared to the non-encapsulated drug and its non-cationic nanoparticle counterpart. This PEI-modified nanoparticle platform represents a promising strategy for enhancing the oral therapeutic efficacy of HEPs. © 2026 Society of Chemical Industry.