Mucoadjuvant properties of lipo- and glycoconjugated derivatives of oligochitosans

• Published in: European journal of medicinal chemistry Vol. 44; no. 5; pp. 2030 - 2037
• Main Authors: Svirshchevskaya, E.V., Alekseeva, L.G., Reshetov, P.D., Phomicheva, N.N., Parphenyuk, S.A., Ilyina, A.V., Zueva, V.S., Lopatin, S.A., Levov, A.N., Varlamov, V.P.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-05-2009
• Subjects: Adjuvants, Immunologic - chemistry; Animals; Antibody Formation - drug effects; Chitin - analogs & derivatives; Chitin - chemistry; Chitin - immunology; Glycoconjugates; Immunoglobulin G - biosynthesis; Lipid chitosan derivatives; Lipids; Low-molecular weight chitosan; Mice; Molecular Weight; Mucoadjuvant; Mucosal immunization; Solubility; Structure-Activity Relationship; DD; Mucoadjuvant; Low-molecular weight chitosan; Gal; LMW-Chi; Lipid chitosan derivatives; Mucosal immunization; LB; Glc-NH 2; Man; HMW-Chi; Glc
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2008.10.007

Chitosan, (1-4)-2-amino-2-deoxy-beta-
d-glucan, is a deacetylated form of chitin, an abundant biodegradable, positively charged natural polysaccharide. Chitosan is used for antigen delivery through mucosal barrier due to its ability to disrupt tight junctions. Here we produced new water-soluble low-molecular weight chitosan (LMW-Chi) lipid derivatives and compared their ability to stimulate humoral response with the effect of unmodified LMW-Chi or its oligosaccharide derivatives. LMW-Chi effectively penetrated into macrophage-like, lymphoid and epithelial cells. It also stimulated in mice IgG production to model proteins delivered either by subcutaneous or intranasal routes. Adjuvant effect of chitosan derivatives was comparable to or lower than that of unmodified LMW-Chi. Thus, it is possible that adjuvant effect is induced by unmodified glucosamine units of chitosan.
The conjugates of low-molecular weight chitosans with fatty acids and carbohydrates were compared for their ability to stimulate IgG response in mice to model proteins delivered via subcutaneous or mucosal routes.
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