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

• Ge Dan

  Graduate School of Pharmaceutical Sciences, Chiba University

• Higashi Kyohei

  Graduate School of Pharmaceutical Sciences, Chiba University

• Ito Daichi

  Graduate School of Pharmaceutical Sciences, Chiba University

• Nagano Kenichi

  Graduate School of Pharmaceutical Sciences, Chiba University

• Ishikawa Ryota

  Graduate School of Pharmaceutical Sciences, Chiba University

• Terui Yusuke

  Faculty of Pharmacy, Chiba Institute of Science

• Higashi Kenjirou

  Graduate School of Pharmaceutical Sciences, Chiba University

• Moribe Kunikazu

  Graduate School of Pharmaceutical Sciences, Chiba University

• Linhardt Robert J.

  Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute

• Toida Toshihiko

  Graduate School of Pharmaceutical Sciences, Chiba University

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.

Journal

• Chemical and Pharmaceutical Bulletin

  Chemical and Pharmaceutical Bulletin 64 (5), 390-398, 2016

  The Pharmaceutical Society of Japan

Keywords

• chondroitin sulfate (CS)
• spermine (SPM)
• poly-ion complex (PIC)
• oral intake
• HPLC

Details

• CRID: 1390001204177277184
• NII Article ID: 130005148753
• NII Book ID: AA00602100
• DOI: 10.1248/cpb.c15-00940
• ISSN: 13475223
• ISSN: 00092363
• NDL BIB ID: 027269876
• PubMed: 27150471
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027269876
• Web Site: https://www.jstage.jst.go.jp/article/cpb/64/5/64_c15-00940/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016381746
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed