| 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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MedLine Citation:
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PMID: 17701325 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 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. 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. |
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Authors:
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Li Wan; Shahriar Pooyan; Peidi Hu; Michael J Leibowitz; Stanley Stein; Patrick J Sinko |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-08-15 |
Journal Detail:
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Title: Pharmaceutical research Volume: 24 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 2007 Nov |
Date Detail:
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Created Date: 2007-09-27 Completed Date: 2007-11-29 Revised Date: 2012-01-18 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 2110-9 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-HIV Agents / administration & dosage* Drug Carriers* Female Macrophages, Peritoneal / metabolism* Male Mice N-Formylmethionine Leucyl-Phenylalanine / administration & dosage*, pharmacokinetics Nanostructures Polyethylene Glycols / administration & dosage*, pharmacokinetics Rats Rats, Sprague-Dawley Tissue Distribution |
| Grant Support | |
ID/Acronym/Agency:
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AI33789/AI/NIAID NIH HHS; AI51214/AI/NIAID NIH HHS; R37 AI051214-05/AI/NIAID NIH HHS; R37 AI051214-06/AI/NIAID NIH HHS; R37 AI051214-07/AI/NIAID NIH HHS; R37 AI051214-08/AI/NIAID NIH HHS; R37 AI051214-11/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Drug Carriers; 0/Polyethylene Glycols; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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