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 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.
Kaminskas
L M
LM
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Wu
Z
Z
Barlow
N
N
Krippner
G Y
GY
Boyd
B J
BJ
Porter
C J H
CJ
D000818:Animals; D002412:Cations / Q000378:metabolism; D002850:Chromatography, Gel; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011107:Polylysine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002412:Cations; D050091:Dendrimers; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D011092:Polyethylene Glycols