Evidence map›Paper›PMID 22743598›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2012

Enhanced anti-HIV efficacy of indinavir after inclusion in CD4-targeted lipid nanoparticles.

Aaron N Endsley, Rodney J Y Ho

Abstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.3field-weighted citation impact, top 22% 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

26 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Review
  3. Leveraging the therapeutic, biological, and self-assembling potential of peptides for the treatment of viral infections.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Review
  4. Review
  5. Nanomedicine based approaches for combating viral infections.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Nanotechnology approaches to eradicating HIV reservoirs.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019
    Review
  13. Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Active targeted drug delivery for microbes using nano-carriers.Current topics in medicinal chemistry · 2015
    Review
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

2 authors at 1 institution in 1 country.

Aaron N EndsleyDepartment of Pharmaceutics, University of Washington, Seattle, WA 98195, USA.
Rodney J Y Ho
University of Washington · US

Funding

YILMA SIV VACCINIA VACCINE TRIALP51RR000166 · NCRR · UNIVERSITY OF WASHINGTON · PI HU, SHIU-LOK · 1985 to 2011
$161.1M
INSTITUTE FOR TRANSLATIONAL HEALTH SCIENCE (UL1): BPCAUL1RR025014 · NCRR · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2007 to 2011
$51.5M
pH Responsive anti-HIV NanoparticlesR01AI077390 · NIAID · UNIVERSITY OF WASHINGTON · PI HO, RODNEY J.Y. · 2009 to 2013
$3.9M
Anti-HIV Drug Targeting to Lymphoid TissuesR01AI052663 · NIAID · UNIVERSITY OF WASHINGTON · PI HO, RODNEY J.Y. · 2003 to 2005
$1.7M
Polymorphism of Multi-Drug-Resistance Protein-1R01GM062883 · NIGMS · UNIVERSITY OF WASHINGTON · PI HO, RODNEY J.Y. · 2002 to 2005
$1.3M
NCRR NIH HHS P51 RR000166NCRR NIH HHS RR00166NCRR NIH HHS RR025014NCRR NIH HHS UL1 RR025014NIAID NIH HHS AI77390NIAID NIH HHS R01 AI052663NIAID NIH HHS R01 AI077390NIGMS NIH HHS R01 GM062883
6 · The paper itself

Abstract

backgroundCombination drug therapy has reduced plasma HIV to undetectable levels; however, drug-sensitive virus persists in patients' lymphoid tissue. We have reported significant lymphoid tissue drug localization with indinavir-associated lipid nanoparticles (LNPs). Our current objective is to evaluate whether additional enhancement is achievable by targeting these particles to CD4-HIV host cells.

methodsWe characterized 2 peptide-coated (CD4-BP2 and CD4-BP4) drug-associated LNPs and demonstrated CD4-cell specificity. Drug-associated LNPs expressing polyethyleneglycol were exposed on HIV-2-infected cells under dynamic conditions that emulated lymph node physiology for 15, 30, and 60 minutes at concentrations from 0 to 25 μM and evaluated for antiviral activity and cell-associated drug concentrations. The specificity of CD4-mediated enhancement of indinavir LNPs antiviral activity was evaluated by blocking with anti-CD4 antibody.

resultsInclusion of CD4-binding peptides on LNPs enhanced antiviral activity for all incubation conditions, compared with control particles or soluble drug (eg, 60 minutes exposure, EC50 = 0.12-0.13 vs. 0.46 μM for targeted nanoparticles vs. soluble drug). The CD4-BP4 peptide exhibited higher efficiency in eliciting antiviral activity than CD4-BP2-coated particles (EC50 = 7.5 μM vs. >25 μM at 15 minutes drug exposure). This enhancement seems to be driven by CD4 availability and cell-associated indinavir concentrations, as blocking of CD4 significantly ablated indinavir efficacy in targeted particles and indinavir concentrations reflected the observed anti-HIV activity.

conclusionsWe constructed CD4-targeted LNPs that provide selective binding and efficient delivery of indinavir to CD4-HIV host cells. Inclusion of polyethyleneglycol in LNPs would minimize immune recognition of peptides. The enhancement of anti-HIV effects is effective even under limited time exposure.

Indexed as

NanoparticlesAnti-HIV AgentsCD4-Positive T-LymphocytesDrug CarriersHIV-2HumansIndinavirLiposomesMicrobial Sensitivity TestsAnti-HIV AgentsDrug CarriersIndinavirLiposomes

Identifiers

PMID22743598
PMCPMC3551348
OpenAlexW2031616185

What OpenQuestion holds

Textmetadata
LicenceTDM
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.