Goal of the research
Two polysaccharides of natural origin, i.e., pullulan and chitosan were studied. Pullulan is a noncharged component of the cell wall of the common yeast-like fungus Aureobasidium pullulans, while chitosan is a cationic polysaccharide obtained by the hydrolysis of chitin, the which is the most abundant by mass polymer in the biosphere. We have synthesized a series of the cationic derivatives of these polysaccharides and studied their physiological action in mice after oral administration. In particular, the influence of the polymers on the cholesterol level in apoE-knockout mice which are an animal model of atherosclerosis, was studied.Results of the research
Chitosan and pullulan were cationically-modified with glycidyltrimethylammonium chloride (GTMAC).
In contrast to unmodified chitosan, cationically-modifed chitosan (HTCC) was well-soluble and easily absorbed after oral administration therefore it showed significantly better bioavailability. It was distributed to lung, heart, and kidneys. It enhanced blood platelet aggregation and decreased erythrocyte deformability. Importantly, it decreased both plasma total cholesterol and LDL-cholesterol levels in apoE-knockout mice and inhibited atherosclerotic plaque development.
Cationically modified pullulan (Pull-GTMAC) showed weak antiproliferative effect towards hepatocytes. In contrast to HTCC, it did not lower the lipid level in serum. In spite of that it was found to reduce the area of atherosclerotic plaque. It is assumed that the atherogenic action of this polymer may be due to the regulation of lipid metabolism genes expression.
Collaboration
Prof. Em. Ryszard Korbut, Jagiellonian University, Collegium Medicum, Chair of Pharmacology