Surface glycosylation of resveratrol-loaded PLGA nanoparticles modulates interfacial interactions with B lymphocytes

Polymeric nanoparticles have emerged as promising platforms for improving the delivery and biological activity of immunomodulatory compounds. In this study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with the monosaccharides mannosamine and galactosamine were developed to explore their interaction with peripheral blood immune cells and their potential as carriers for the immunomodulatory compound trans-resveratrol. Monosaccharide conjugation to PLGA was achieved through carbodiimide-mediated coupling, and the nanoparticles were prepared by nanoprecipitation using Pluronic F127. The resulting nanoparticles exhibited spherical morphology, hydrodynamic diameters ranging from 160 to 231 nm, ζ-potential values between -33 and -43 mV, polydispersity indices below 0.13, and trans-resveratrol encapsulation efficiencies above 50%. Release studies showed a sustained and predominantly diffusion-controlled profile. The nanoparticles showed preferential association with CD19^⁺ B lymphocytes compared with other circulating immune populations. This interaction was significantly enhanced by monosaccharide functionalization, particularly in galactosamine-modified systems. Cytotoxicity assays demonstrated minimal effects on membrane integrity and mitochondrial potential in peripheral blood mononuclear cells. Furthermore, these nanoparticles inhibited surface marker activation, cell proliferation, and the differentiation of B cells into plasma cells. Overall, these results indicate that monosaccharide-functionalized PLGA nanoparticles promote selective targeting of B lymphocytes while maintaining favorable biocompatibility and physicochemical properties. This behavior highlights the role of surface glycosylation in modulating nanoparticle-cell interactions, supporting their potential as nanocarriers for immunomodulatory applications.