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Enhanced Immunomodulatory Activity of Gelatin-Encapsulated Rubus coreanus Miquel Nanoparticles
Department of Biomaterials Engineering, Kangwon National University, Chuncheon 200-701, Korea
Medical & Bio-material Research Center, Kangwon National University, Chuncheon 200-701, Korea
Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA, Eumseong 369-873, Korea
Bionanoscience and Bio-Imaging Program, Cellular Stress and Ageing Program, Bio&Nano-Solutions, D-40472 Düsseldorf, Germany
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 24 November 2011; Accepted: 29 November 2011 / Published: 7 December 2011
Abstract: The aim of this work was to investigate the immunomodulatory activities of Rubus coreanus 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 Rubus coreanus-gelatin nanoparticles and in general ~2–3 times higher than control and on average ~2 times higher than ferulic acid. R. coreanus-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. In vivo immunomodulatory activity in mice fed with R. coreanus-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 Rubus coreanus 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.
Keywords: Rubus coreanus Miquel; nano-encapsulation process; nanoparticle; immune activity; immunomodulation; edible polymer; gelatin; ferulic acid; cytotoxicity
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Seo, Y.C.; Choi, W.Y.; Lee, C.G.; Cha, S.W.; Kim, Y.O.; Kim, J.-C.; Drummen, G.P.C.; Lee, H.Y. Enhanced Immunomodulatory Activity of Gelatin-Encapsulated Rubus coreanus Miquel Nanoparticles. Int. J. Mol. Sci. 2011, 12, 9031-9056.
Seo YC, Choi WY, Lee CG, Cha SW, Kim YO, Kim J-C, Drummen GPC, Lee HY. Enhanced Immunomodulatory Activity of Gelatin-Encapsulated Rubus coreanus Miquel Nanoparticles. International Journal of Molecular Sciences. 2011; 12(12):9031-9056.
Seo, Yong Chang; Choi, Woon Yong; Lee, Choon Geun; Cha, Seon Woo; Kim, Young Ock; Kim, Jin-Chul; Drummen, Gregor P. C.; Lee, Hyeon Yong. 2011. "Enhanced Immunomodulatory Activity of Gelatin-Encapsulated Rubus coreanus Miquel Nanoparticles." Int. J. Mol. Sci. 12, no. 12: 9031-9056.