articles The Impact of Molecular Weight and PEG Chain Length on the Systemic Pharmacokinetics of PEGylated Poly L-Lysine Dendrimers Lisa M. Kaminskas,† Ben J. Boyd,† Peter Karellas,†,‡ Guy Y. Krippner,‡ Romina Lessene,‡ Brian Kelly,‡ and Christopher J. H. Porter*,† Department of Pharmaceutics, Victorian College of Pharmacy, Monash UniVersity, 381 Royal Parade, ParkVille, VIC, Australia, and Starpharma Holdings Ltd., LeVel 6, Baker Heart Research Building, Commercial Road, Melbourne, VIC, Australia Received September 9, 2007; Revised Manuscript Received January 15, 2008; Accepted January 25, 2008
Abstract: The impact of PEGylation on the pharmacokinetics and biodistribution of 3H-labeled poly L-lysine dendrimers has been investigated after intravenous administration to rats. The volumes of distribution, clearance and consequently the plasma half-lives of the PEGylated dendrimers were markedly dependent on the total molecular weight of the PEGylated dendrimer, but were not specifically affected by the PEG chain length alone. In general, the larger dendrimer constructs (i.e. >30 kDa) had reduced volumes of distribution, were poorly renally cleared and exhibited extended elimination half-lives (t1/2 1–3 days) when compared to the smaller dendrimers (i.e.
