Periodical
The Impact of Molecular Weight and PEG Chain Length on the Systemic Pharmacokinetics of PEGylated Poly l-Lysine Dendrimers
| العنوان: | The Impact of Molecular Weight and PEG Chain Length on the Systemic Pharmacokinetics of PEGylated Poly l-Lysine Dendrimers |
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| المؤلفون: | M. Kaminskas, Lisa, J. Boyd, Ben, Karellas, Peter, Y. Krippner, Guy, Lessene, Romina, Kelly, Brian, J. H. Porter, Christopher |
| المصدر: | Molecular Pharmaceutics; May 2008, Vol. 5 Issue: 3 p449-463, 15p |
| مستخلص: | 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 ( t1/21–3 days) when compared to the smaller dendrimers (i.e. <20 kDa) which were rapidly cleared from the plasma principally into the urine ( t1/21–10 h). At later time points the larger dendrimers concentrated in the organs of the reticuloendothelial system (liver and spleen); however, the absolute extent of accumulation was low. Size exclusion chromatography of plasma and urine samples revealed that the PEGylated dendrimers were considerably more resistant to biodegradation in vivo than the underivatized poly l-lysine dendrimer cores. The results suggest that the size of PEGylated poly l-lysine dendrimer complexes can be manipulated to optimally dictate their pharmacokinetics, biodegradation and bioresorption behavior. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 15438384 15438392 |
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| DOI: | 10.1021/mp7001208 |