Pharmaceutical Research

, Volume 24, Issue 11, pp 2110–2119

Peritoneal Macrophage Uptake, Pharmacokinetics and Biodistribution of Macrophage-Targeted PEG-fMLF (N-Formyl-Methionyl-Leucyl-Phenylalanine) Nanocarriers for Improving HIV Drug Delivery

  • Li Wan
  • Shahriar Pooyan
  • Peidi Hu
  • Michael J. Leibowitz
  • Stanley Stein
  • Patrick J. Sinko
Research Paper

DOI: 10.1007/s11095-007-9402-5

Cite this article as:
Wan, L., Pooyan, S., Hu, P. et al. Pharm Res (2007) 24: 2110. doi:10.1007/s11095-007-9402-5

Abstract

Purpose

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

Methods

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.

Results

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 t1/2 of PEG5K by threefold but decreased the t1/2 of PEG20K 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.

Conclusions

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.

Key words

biodistributionHIVPEG-fMLF nanocarrierperitoneal macrophagepharmacokinetic

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Li Wan
    • 1
  • Shahriar Pooyan
    • 1
  • Peidi Hu
    • 1
  • Michael J. Leibowitz
    • 2
    • 3
  • Stanley Stein
    • 1
  • Patrick J. Sinko
    • 1
    • 3
    • 4
  1. 1.Department of Pharmaceutics, Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayUSA
  2. 2.Department of Molecular Genetics, Microbiology & ImmunologyUniversity of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical SchoolPiscatawayUSA
  3. 3.Cancer Institute of New JerseyNew BrunswickUSA
  4. 4.Environmental and Occupational Health Science InstitutePiscatawayUSA