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.

Health effects of dietary sulfated polysaccharides from seafoods and their interaction with gut microbiota

“…In addition to MW, the high charge density and hydrophilicity of SPs also significantly affect their bioaccessibility/bioavailability and health effects (Baici et al., 1992). Recent studies have attempted to reduce the negative charge and hydrophilicity of SPs through electrostatic interaction and conjugation effect, thereby increasing their oral bioavailability and enhancing the health effects (Ge et al., 2016; Xiao, Fei, et al., 2014. In particular, CS possessed nearly neutral surface charge after it was combined with polyamines through electrostatic interaction, which remarkably improved its oral bioavailability (Ge et al., 2016).…”

“…Recent studies have attempted to reduce the negative charge and hydrophilicity of SPs through electrostatic interaction and conjugation effect, thereby increasing their oral bioavailability and enhancing the health effects (Ge et al., 2016; Xiao, Fei, et al., 2014. In particular, CS possessed nearly neutral surface charge after it was combined with polyamines through electrostatic interaction, which remarkably improved its oral bioavailability (Ge et al., 2016). CS conjugation with α‐linolenic acid could improve its hydrophobicity, which could produce a positive synergistic effect on its anti‐inflammation and antiatherosclerosis effects (Xiao et al., 2014).…”

Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin

“…If the two layers were thoroughly mixed again using a vortex mixer, the original PIC suspension could be restored. Morphological characterization of the PIC suspension from heparin (10 mg/mL) and 10 mM SPM showed that it was spherical in shape and in a micrometer size range ( Figure 1 B), correlating closely with the particle size (0.57 ± 0.25 μm) measured by dynamic light scattering ( Table 1 ) [ 22 ].

Figure 1 PIC formation efficiency was influenced by mixing concentration ratio of heparin and polyamines, the molecular weight of heparin.

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“…Equivalent volumes of solutions of heparin and polyamines were then mixed to generate the PIC. The PIC formation efficiency, effect of pH value on the stability of PIC, determination of particle size and ζ-potential, surface structure analysis were evaluated as described previously [ 22 ]. Low molecular weight heparin was obtained by photochemical depolymerization with titanium dioxide (TiO 2 ) [ 23 ].…”

“…Taa, in particular, stabilizes nucleic acid and protects it against depurination more effectively than SPM [ 20 , 21 ]. We have previously shown that poly-ion complex (PIC), generated in aqueous solutions through the electrostatic interaction of chondroitin sulfate (CS) and polyamines, improves the oral bioavailability of CS [ 22 ].…”