title: Poly-ion Complex of Chondroitin Sulfate and Spermine and Its Effect on Oral Chondroitin Sulfate Bioavailability.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University.
authors.forename: Dan
authors.initials: D
authors.lastname: Ge
authors.forename: Kyohei
authors.initials: K
authors.lastname: Higashi
authors.forename: Daichi
authors.initials: D
authors.lastname: Ito
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nagano
authors.forename: Ryota
authors.initials: R
authors.lastname: Ishikawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Terui
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010316:Particle Size; D013096:Spermine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D013096:Spermine; D002809:Chondroitin Sulfates