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Microfluidic synthesis of ginseng polysaccharide nanoparticles for immunostimulating action on Macrophage cell lines Kazi Farida Akhter, Md Abdul Mumin, Ed Lui , and Paul A. Charpentier ACS Biomater. Sci. Eng., Just Accepted Manuscript • DOI: 10.1021/acsbiomaterials.5b00413 • Publication Date (Web): 06 Nov 2015 Downloaded from http://pubs.acs.org on November 28, 2015
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ACS Biomaterials Science & Engineering
Microfluidic Synthesis of Ginseng Polysaccharide Nanoparticles for Immunostimulating Action on Macrophage Cell Lines
Kazi Farida Akhtera, Md Abdul Mumina, Edmond K. Luib, Paul A. Charpentiera*
a
b
Chemical and Biochemical Engineering, Physiology and Pharmacology, University of Western Ontario, London Ontario, Canada N6A 5B9
*To whom all correspondence should be addressed: email:
[email protected]; Tel: (519) 661-3466; Fax: (519) 661-3498
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ABSTRACT North American (NA) ginseng root (Panax quinquefolium) has become of increasing scientific interest due to its immune-enhancing properties. Herein, we have developed a novel approach to synthesize ginseng polysaccharide nanoparticles (NPs) from NA ginseng for enhancing their immunostimulation. Nanoparticles of ginseng polysaccharide were prepared using a microfluidic device and compared to other conventional wet chemical processes including nanoprecipitation and reverse microemulsion. The morphology and size of the NPs were characterized by SEM, TEM, DLS and FTIR. Depending on the experimental conditions, microfluidics was found to provide unimodal polysaccharide spheres down to 20 nm (±4nm) with very narrow particle size distributions. In addition, the immunostimulating effect of the polysaccharide NPs was investigated on Murine macrophage cell lines, with the results revealing an enhanced production of all proinflammatory mediators in a concentration dependent manner. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of producing ginseng polysaccharide NPs with demonstrated enhancement of immunostimulation of macrophage cell lines.
KEYWORDS: Nanoparticles, Ginseng polysaccharide, Nanoprecipitation, Microfluidics, Macrophage cell lines
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ACS Biomaterials Science & Engineering
INTRODUCTION Ginseng is an important source of plant polysaccharides that belongs to the Araliaceae family. The two most commonly recognized species of ginseng are Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolium). In the last two decades, ginseng has become the second-highest selling herbal medicine in North America, being used as a supplement for enhancement of immunity, stress relief, prevention of aging, cardiovascular diseases,
HIV etc.1-4 Polysaccharides, the major medicinal fractions derived from ginseng
(Panax quinquefolium) root, have been shown to provide immune-modulating effects.
5-10
In
particular, COLD-FX®, a commercially available natural health product isolated from North American ginseng root, contains 80% poly-furanosyl-pyranosyl-saccharides, and has been clinically used for the prevention of upper respiratory tract infections.
3,11
Macrophage cells
have been found the most important components of host defense against bacterial infections, neoplastic cells, killing tumor cells etc
12,13
. Under physiological conditions, polysaccharides
stimulate the activity of macrophages and enhance the production of different mediators or active components, such as interferon-γ, tumor necroses factor (TNF)- α, interleukin (IL)- 1,2,6, nitrite etc. 5,6,9,10 Recently, significant work has been carried out by various research groups on the immune stimulation effect of ginseng polysaccharide extracts on macrophage cell lines.
3,14-17
It
has been found that due to their large aggregate size, a significant portion of these macromolecules cannot pass the cell barrier of the gastrointestinal tract.18 Nowadays, nanotechnology in medicine (or nanomedicine) is being actively used for rational and targeted delivery of pharmaceutical, therapeutic, and diagnostic agents to specific cells and extracellular elements of the body.19-21 The possible mechanisms for the nanoparticles to pass through the 3 ACS Paragon Plus Environment
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gastrointestinal (and other physiological) barriers include: (1) paracellular passage—particles “kneading” between intestinal epithelial cells due to their extremely small size (
