Enhanced Immunomodulatory Activity of Gelatin-Encapsulated <i>Rubus coreanus</i> Miquel Nanoparticles

다국어 초록 (Multilingual Abstract)

<P>The aim of this work was to investigate the immunomodulatory activities of <I>Rubus coreanus</I> Miquel extract-loaded gelatin nanoparticles. The mean size of the produced nanoparticles was 143 ± 18 nm with a bandwidth of 76 nm in the size distribution and a maximum size of ~200 nm, which allows effective nanoparticle uptake by cells. Confocal imaging confirmed this, since the nanoparticles were internalized within 30 min and heterogeneously distributed throughout the cell. Zeta-potential measurements showed that from pH = 5 onwards, the nanoparticles were highly negatively charged, which prevents agglomeration to clusters by electrostatic repulsion. This was confirmed by TEM imaging, which showed a well dispersed colloidal solution. The encapsulation efficiency was nearly 60%, which is higher than for other components encapsulated in gelatin nanoparticles. Measurements of immune modulation in immune cells showed a significant effect by the crude extract, which was only topped by the nanoparticles containing the extract. Proliferation of B-, T- and NK cells was notably enhanced by <I>Rubus coreanus</I>-gelatin nanoparticles and in general ~2–3 times higher than control and on average ~2 times higher than ferulic acid. <I>R. coreanus</I>-gelatin nanoparticles induced cytokine secretion (IL-6 and TNF-α) from B- and T-cells on average at a ~2–3 times higher rate compared with the extract and ferulic acid. <I>In vivo</I> immunomodulatory activity in mice fed with <I>R. coreanus</I>-gelatin nanoparticles at 1 mL/g body weight showed a ~5 times higher antibody production compared to control, a ~1.3 times higher production compared to the extract only, and a ~1.6 times higher production compared to ferulic acid. Overall, our results suggest that gelatin nanoparticles represent an excellent transport vehicle for <I>Rubus coreanus</I> extract and extracts from other plants generally used in traditional Asian medicine. Such nanoparticles ensure a high local concentration that results in enhancement of immune cell activities, including proliferation, cytokine secretion, and antibody production.</P>