Evidence map›Paper›PMID 18092743›Full record

ArticleBioconjugate chemistry2008

Optimizing size and copy number for PEG-fMLF (N-formyl-methionyl-leucyl-phenylalanine) nanocarrier uptake by macrophages.

Li Wan, Xiaoping Zhang, Shahriar Pooyan, Matthew S Palombo, Michael J Leibowitz, Stanley Stein, Patrick J Sinko

Open access · greenAbstract read
In one paragraph

Article in Bioconjugate chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Design and evaluation of a CXCR4 targeting peptide 4DV3 as an HIV entry inhibitor and a ligand for targeted drug delivery.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019
    Article
  4. Article
  5. Review
  6. Article
  7. Targeting strategies for delivery of anti-HIV drugs.Journal of controlled release : official journal of the Controlled Release Society · 2014
    Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Stimuli-responsive star poly(ethylene glycol) drug conjugates for improved intracellular delivery of the drug in neuroinflammation.Journal of controlled release : official journal of the Controlled Release Society · 2010
    Article
  13. Review
  14. Review
  15. Article
  16. Prodrug and conjugate drug delivery strategies for improving HIV/AIDS therapy.Journal of drug delivery science and technology · 2009
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Li WanDepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.
Xiaoping Zhang
Shahriar Pooyan
Matthew S Palombo
Michael J Leibowitz
Stanley Stein
Patrick J Sinko
Rutgers, The State University of New Jersey · US

Funding

Enhancing Intestinal & Brain Uptake of Anti-AIDS DrugsR37AI051214 · NIAID · RUTGERS, THE STATE UNIV OF N.J. · PI SINKO, PATRICK J. · 2006 to 2015
$4.4M
Enhancing Intestinal &Brain Uptake of Anti-AIDS Drugs.R01AI051214 · NIAID · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI SINKO, PATRICK J. · 2002 to 2005
$1.1M
ORAL ABSORPTION AND BIOPHARMACEUTICS OF ANTI-HIV DRUGSR29AI033789 · NIAID · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI SINKO, PATRICK J. · 1993 to 1997
–
NIAID NIH HHS AI 33789NIAID NIH HHS AI 51214NIAID NIH HHS R01 AI051214NIAID NIH HHS R37 AI051214
6 · The paper itself

Abstract

Curing HIV-1 infection has remained elusive because of low and fluctuating drug levels arising from poor absorption, the development of viral reservoirs and sanctuary sites, toxicity, and patient nonadherence. The present study addresses the issue of insufficient drug exposure in macrophages. Viral reservoir sites such as macrophages are believed to be responsible for the viral rebound effect observed upon the discontinuation of anti-HIV drug therapy. In our proposed model, a drug can be covalently attached to a nanocarrier in order to facilitate the delivery of therapeutic agents to the site(s) of infection. As an initial step, we propose the covalent attachment of several copies of N-formyl-Met-Leu-Phe (fMLF), a known chemo-attractant for macrophages. In this article, one or more copies of fMLF were conjugated to multifunctional commercially available or novel, peptide-based PEG nanocarriers in which the structure was varied by appending PEGs with average molecular weights of 5, 20, and 40 kDa. U937 cell-specific binding and cellular uptake were analyzed. The results of uptake studies indicate that (i) uptake is energy dependent and mediated by a fMLF receptor, (ii) appending only 2 copies of the targeting ligand to the multifunctional nanocarrier appears sufficient for binding in vitro, and (iii) of the three configurations studied, the nanocarrier with a molecular weight of about 20 kDa, corresponding to a size of 20-60 nm, demonstrated the highest uptake. The results of the current studies demonstrate the feasibility of targeting macrophages and the suitability of using these synthetically versatile peptide--backbone PEG nanocarriers. The convenience, flexibility and possible limitations of this nanocarrier approach are discussed.

Indexed as

AnimalsAnti-HIV AgentsCell DifferentiationDrug CarriersHumansMacrophagesMicroscopy, FluorescenceNanostructuresN-Formylmethionine Leucyl-PhenylalaninePolyethylene GlycolsRabbitsReceptors, Formyl PeptideTemperatureTime FactorsU937 CellsAnti-HIV AgentsDrug CarriersN-Formylmethionine Leucyl-PhenylalaninePolyethylene GlycolsReceptors, Formyl Peptide

Identifiers

PMID18092743
PMCPMC2729117
OpenAlexW1993661137

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.