epiglucan and hydrazine

Chitosan and β-glucan are substances that are very widely used in the pharmaceutical and food industries, medicine and other areas. These polysaccharides have immense significance in human metabolism. They are able to affect the levels of cholesterol and lipids. Chemical modification of these polysaccharides allows the support of these attributes. A main goal is to prepare a group of amide derivatives of carboxymethyl chitosan and carboxymethyl β-glucan to obtain a new group of polysaccharide derivatives and increase the benefits and attributes of these polysaccharides. The aim of carboxymethylation and subsequent two-step amidation is to achieve a high degree of substitution in the prepared derivatives. The amidation consisted methyl esterification followed by amino-de-alkoxylation with amidation reagents (n-alkylamines, hydrazine and hydroxylamine). The purity and substitution degree of the prepared derivatives were monitored by vibration spectroscopic methods (FTIR and FT Raman) and organic elemental analysis. The main, which was due to the presence of a secondary component (chitin) of polysaccharides, was the calculation of the substitution degree, which was based on the organic elemental analysis in combination with FTIR spectroscopy. These analytic methods confirmed the preparation of the substituted N-alkylamides, hydrazide and hydroxamic acid of carboxymethyl chitosan and carboxymethyl β-glucan.

Topics: Animals; beta-Glucans; Chitin; Chitosan; Esterification; Humans; Hydrazines; Hydrophobic and Hydrophilic Interactions; Polysaccharides; Spectroscopy, Fourier Transform Infrared

The diseases caused by Zika virus (ZIKV) have received widespread concerns. As a key viral element of ZIKV, E protein was an ideal antigen for vaccine development. However, the poor immunogenicity of E protein necessitated the formulation with adjuvants. Formulation of E protein by conjugation with β-glucan was a strategy to improve the immunogenicity of E protein, where β-glucan was a polysaccharide adjuvant that could activate macrophages and trigger intracellular processes. However, the antigenic epitopes of E protein and the immunomodulatory sites of β-glucan were shielded in the conjugate. Moreover, the conjugate might elicit the undesired immune response to β-glucan. Thus, the acidic-labile hydrazone and the thiol-sensitive disulfide bonds were used as the linkers between E protein and β-glucan. Hydrazone hydrolysis and disulfide reduction could sufficiently detach the two components in the immune cells to overcome the two disadvantages. As compared with the conjugate without the two linkers, the conjugate with the two linkers (E-PS-4) elicited high E protein-specific IgG titers and low β-glucan-specific IgG titers. E-PS-4 elicited high levels of IFN-γ, TNF-α, IL-2, and IL-10. Moreover, E-PS-4 greatly facilitated the activation of dendritic cells without significant toxicity to the organs. A pharmacokinetic study revealed that the serum duration of E-PS-4 was longer than that of E protein. Accordingly, conjugation of E protein with β-glucan by the hydrazone and disulfide linkers could promote a potent cellular and humoral immune response to E protein. Thus, our study could facilitate the development of an effective vaccine against ZIKV.

Topics: Animals; beta-Glucans; Dynamic Light Scattering; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Hydrazines; Hydrazones; Interferon-gamma; Interleukin-10; Interleukin-2; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Rats; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Tumor Necrosis Factor-alpha; Zika Virus; Zika Virus Infection