Abstract
Disposition characteristics of three types of cationized proteins, cationized superoxide dismutase (cSOD, molecular weight 34 kDa), cationized bovine serum albumin (cBSA, molecular weight 70 kDa), and cationized uricase (cUC, molecular weight 130 kDa) after intravenous injection were studied in mice. [111IN]cBSA and [111In]cUC could be taken up by the liver up to more than 40–60% of dose within 60 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 25% of dose for [111In]cSOD. On the other hand, [111In]cSOD were significantly accumulated into the kidney up to 70% of dose within 60 min. Pharmacokinetic analysis revealed that hepatic uptake clearances of [111In]cSOD, [111In]cBSA and [111In]cUC were 71.1-, 709-, and 11.2-fold higher than those of 111In-unmodified proteins, respectively. Similar results were observed for urinary excretion clearance including kidney accumulation clearance. It was concluded that cationization of protein drugs might play an important role in their hepatic and kidney uptake and offer a promising approach to controlling the pharmacokinetic characteristics of protein drugs.
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