The impact of molecular weight and PEG chain length on the systemic pharmacokinetics of pegylated poly L-lysine dendrimers

The impact of PEGylation on the pharmacokinetics and biodistribution of 3H-labeled poly L-lysine dendrimers has been investrigated after intravenous administration to rats. The volumes of distribtuion, clearance and consequentrly the plasma half-lives of the PEGylated dendirmers were markedly dependent ont he total molecular weight of the PEGylated dendirmer, but were not specifically affectd byt eh PEG chain lenght alone. In general, the larger dendrimer constructs (i.e. >30KDa)had reduced volumes of distribtuion, were poorly renally cleared and exhibited extended elimination half-lives (t1/2 1-3 days) when compared to the smaller dendrimers (i.e.