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 investigated after intravenous administration to rats. The volumes of distribution, clearance and consequently the plasma half-lives of the PEGylated dendrimers were markedly dependen...

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Bibliographic Details
Published in:Molecular pharmaceutics 2008-05, Vol.5 (3), p.449-463
Main Authors: Kaminskas, Lisa M, Boyd, Ben J, Karellas, Peter, Krippner, Guy Y, Lessene, Romina, Kelly, Brian, Porter, Christopher J. H
Format: Article
Language:English
Subjects:
Animals
Biological Availability
Dendrimers - administration & dosage
Dendrimers - chemical synthesis
Dendrimers - pharmacokinetics
Drug Delivery Systems - methods
Half-Life
Injections, Intravenous
Male
Metabolic Clearance Rate
Molecular Structure
Molecular Weight
Polyethylene Glycols - pharmacokinetics
Polylysine - administration & dosage
Polylysine - blood
Polylysine - pharmacokinetics
Polylysine - urine
Rats
Rats, Sprague-Dawley
Tissue Distribution
Tritium
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Summary: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 (t 1/2 1–3 days) when compared to the smaller dendrimers (i.e.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp7001208