Poly-ion Complex of Chondroitin Sulfate and Spermine and its Effect on Oral Chondroitin Sulfate Bioavailability

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Authors
Ge, Dan
Higashi, Kyohei
Ito, Daichi
Nagano, Kenichi
Ishikawa, Ryota
Terui, Yusuke
Higashi, Kenjirou
Moribe, Kunikazu
Linhardt, Robert J.
Toida, Toshihiko
Issue Date
2016-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Chondroitin sulfate (CS) has been accepted as an ingredient in health foods for the treatment of symptoms related to arthritis and cartilage repair. However, CS is poorly absorbed through the gastrointestinal tract because of its high negative electric charges and molecular weight (MW). In this study, poly-ion complex (PIC) formation was found in aqueous solutions through electrostatic interaction between CS and polyamines-organic molecules having two or more primary amino groups ubiquitously distributed in natural products at high concentrations. Characteristic properties of various PICs generated by mixing CS and natural polyamines, including unusual polyamines, were studied based on the turbidity for PIC formation, the dynamic light scattering for the size of PIC particles, and ζ-potential measurements for the surface charges of PIC particles. The efficiency of PIC formation between CS and spermine increased in a CS MW-dependent manner, with 15 kDa CS being critical for the formation of PIC (particle size: 3.41 µm) having nearly neutral surface charge (ζ-potential: -0.80 mV). Comparatively, mixing tetrakis(3-aminopropyl)ammonium and 15 kDa of CS afforded significant levels of PIC (particle size: 0.42±0.16 µm) despite a strongly negative surface charge (-34.67±1.15 mV). Interestingly, the oral absorption efficiency of CS was greatly improved only when PIC possessing neutral surface charges was administered to mice. High formation efficiency and electrically neutral surface charge of PIC particles are important factors for oral CS bioavailability.
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Bulletins of the Japanese Pharmaceutical Society, 64, 390–398
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Full Citation
Poly-ion Complex of Chondroitin Sulfate and Spermine and its Effect on Oral Chondroitin Sulfate Bioavailability, D. Ge, K. Higashi, D. Ito, Y. Terui K. Nagano, R. Ishikawa, K. Higashi, K. Moribe, R. J. Linhardt, T. Toida, Bulletins of the Japanese Pharmaceutical Society, 64, 390–398, 2016.
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ISSN
13475223
92363
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