Body distribution profile of polysaccharides after intravenous administration

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Abstract
The body distribution of pullulan and dextran, which are nonionic polysaccharides, was studied. After intravenous injection of 125I-labeled polysaccharides with different molecular weights, the half-life period in the blood circulation and the body distribution were pharmacokinetically investigated and compared with those of polyethylene glycol (PEG) and polyvinyl alcohol (PVA). Polysaccharides of higher molecular weights circulated in the bloodstream for a longer period than those of lower molecular weights. The half-life period of pullulan ranged from 15 to 90 min, changing remark-ably around molecular weight 30,000, and was shorter than that of dextran. Body distribution studies demonstrated that pullulan tended to accumulate in the liver to a greater extent than dextran, whereas PEG and PVA were hardly disposed there. This preferable accumulation of polysaccharides in the liver was observed over the whole molecular weight range studied. Eighty percent of pullulan with large molecular weights was localized in the liver without any accumulation in other organs, suggesting an inherent affinity of pullulan for the liver. In addition, the excretion clearance of pullulan and dextran decreased with an increase in molecular weight, although the clearance of pullulan was smaller than that of dextran over the high-molecularweight range. It is likely that the remarkable affinity of pullulan for liver causes a short half-life period in the circulation compared with that of dextran. These findings indicate that pullulan is promising as a polymeric carrier for drugs targeted to the liver.