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• W2055366590 abstract "Cationic poly-l-lysine 3H-dendrimers with either 16 or 32 surface amine groups (BHALys [Lys]4 [3H-Lys]8 [NH2]16 and BHALys [Lys]8 [3H-Lys]16 [NH2]32, generation 3 and 4, respectively) have been synthesized and their pharmacokinetics and biodistribution investigated after intravenous administration to rats. The species in plasma with which radiolabel was associated was also investigated by size exclusion chromatography (SEC). Rapid initial removal of radiolabel from plasma was evident for both dendrimers (t1/2 < 5 min). Approximately 1 h postdose, however, radiolabel reappeared in plasma in the form of free lysine and larger (but nondendrimer) species that coeluted with albumin by SEC. Plasma and whole blood pharmacokinetics were similar, precluding interaction with blood components as a causative factor in either the rapid removal or reappearance of radioactivity in plasma. Administration of monomeric 3H l-lysine also resulted in the appearance in plasma of a radiolabeled macromolecular species that coeluted with albumin by SEC, suggesting that biodegradation of the dendrimer to l-lysine and subsequent bioresorption may explain the pharmacokinetic profiles. Capping the Lys8 dendrimer with d-lysine to form BHALys [Lys]4 [3H-Lys]8 [d-Lys]16 [NH2]32 resulted in similar, and very rapid, initial disappearance kinetics from plasma when compared to the l-lysine capped dendrimer. Since significant extravasation of these large hydrophilic molecules seems unlikely, this most likely reflects both elimination and extensive binding to vascular surfaces. Capping with “non-natural” d-lysine also appeared to render the dendrimer essentially inert to the biodegradation process. For the l-lysine capped dendrimers, radiolabel was widely distributed throughout the major organs, with no apparent selectivity for organs of the reticuloendothelial system. In contrast, a greater proportion of the administered radiolabel was recovered in the organs of the reticuloendothelial system for the d-lysine capped system, as might be expected for a nondegrading circulating foreign colloid. To our knowledge this is the first data to demonstrate the biodegradation/bioresorption of poly-l-lysine dendrimers and has significant implications for the utility of these systems as drugs or drug delivery systems. Keywords: Dendrimer; pharmacokinetics; poly-l-lysine; biodegradation; biodistribution" @default.
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• W2055366590 date "2006-08-04" @default.
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• W2055366590 title "Cationic Poly-<scp>l</scp>-lysine Dendrimers: Pharmacokinetics, Biodistribution, and Evidence for Metabolism and Bioresorption after Intravenous Administration to Rats" @default.
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• W2055366590 doi "https://doi.org/10.1021/mp060032e" @default.
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