Partly-PEGylated Poly-L-lysine Dendrimers Have Reduced Plasma Stability and Circulation Times Compared With Fully PEGylated Dendrimers

The current study was performed to examine the effect of 50% surface PEGylation on the plasma circulation, biodistribution and metabolism of intravenously administered Generation 4 poly-L-lysine dendrimers in rats. Partial surface PEGylation blocked the rapid and extensive vascular binding previousl...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2009-10, Vol.98 (10), p.3871-3875
Main Authors: Kaminskas, L.M., Wu, Z., Barlow, N., Krippner, G.Y., Boyd, B.J., Porter, C.J.H.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cations - metabolism
Chromatography, Gel
dendrimer
Dendrimers - chemistry
Dendrimers - pharmacokinetics
General pharmacology
Injections, Intravenous
Male
Medical sciences
metabolism
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
poly-L-lysine
Polyethylene Glycols - chemistry
Polyethylene Glycols - pharmacokinetics
Polylysine - analogs & derivatives
Polylysine - blood
Polylysine - chemistry
Polylysine - pharmacokinetics
Rats
Rats, Sprague-Dawley
Tissue Distribution
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Summary:The current study was performed to examine the effect of 50% surface PEGylation on the plasma circulation, biodistribution and metabolism of intravenously administered Generation 4 poly-L-lysine dendrimers in rats. Partial surface PEGylation blocked the rapid and extensive vascular binding previously described for the non-PEGylated dendrimer and slowed metabolism of the core, however the effect was less than that observed for total surface coverage of PEG. Capping the residual surface amines with acetyl groups further improved plasma stability. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3871–3875, 2009
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.21692