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Pharm Res. 2007 Nov;24(11):2110-9. Epub 2007 Aug 15.

Peritoneal macrophage uptake, pharmacokinetics and biodistribution of macrophage-targeted PEG-fMLF (N-formyl-methionyl-leucyl-phenylalanine) nanocarriers for improving HIV drug delivery.

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  • 1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.



To assess in vivo macrophage targeting potential of PEG-fMLF nanocarriers and to investigate their biodistribution, peritoneal macrophage uptake, and pharmacokinetics.


Multiple copies of fMLF were conjugated to purchased and novel (branched, peptide-based) PEG nanocarriers. Peritoneal macrophage uptake was evaluated in mice 4 hours after IP administration of fluorescence-labeled PEG-fMLF nanocarriers. Pharmacokinetics and biodistribution were determined in rats after IV administration of tritiated PEG-fMLF nanocarriers.


Attachment of one, two, or four fMLF copies increased uptake in macrophages by 3.8-, 11.3-, and 23.6-fold compared to PEG without fMLF. Pharmacokinetic properties and tissue distribution also differed between nanocarriers with and without fMLF. Attachment of fMLF residues increased the t(1/2) of PEG(5K) by threefold but decreased the t(1/2) of PEG(20K) by 40%. Attachment of fMLF increased accumulation of nanocarriers into macrophages of liver, kidneys and spleen. However, on a molar basis, penetration was equivalent suggesting nanocarrier size and targeting moieties are important determinants.


These results demonstrate the feasibility for targeting macrophages, a primary HIV reservoir site. However, these studies also suggest that balancing peripheral tissue penetration (a size-dependent phenomenon) versus target cell uptake specificity remains a challenge to overcome.

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