Electric Charge Influence of Dextran Derivatives on their Tumor Accumulation After Intravenous Injection

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Abstract
The objective of the present study is to investigate the profile of tumor accumulation of electrically charged dextran derivatives intravenously injected and to compare it with that of noncharged dextran. Diethylaminoethyl and sulfoethyl groups were introduced into dextran to prepare positively and negatively charged derivatives. Following intravenous injection of the dextran derivatives to mice carrying a footpad tumor mass, whole-body distribution was examined to pharmacokinetically analyze the dependence on the substitution extent of charged groups and the molecular weight of dextran derivatives. Cationization shortened the plasma half-life of dextran, while anionization prolonged it. Both non-charged and negatively charged dextrans had a prolonged half-life proportionate to the molecular weight, whereas the half-life of positively charged dextran was not influenced by molecular weight. Dextran derivatives accumulated in tumor tissue to a significantly higher extent than in normal tissue, irrespective of the charge type, substitution extent, and molecular weight. The high tumor accumulation tended to be reduced with an increase in the substitution extent of cationic groups, but anionic derivatization had no effect. Cationic dextrans had an increased liver clearance, which, in turn, caused their reduced tumor accumulation. It was concluded that every type of dextran derivative was significantly susceptible to tumor accumulation, depending on the charge density and dextran molecular weight.