Evidence map›Paper›PMID 31725756›Full record

ArticlePloS one2019

Importance of thorough tissue and cellular level characterization of targeted drugs in the evaluation of pharmacodynamic effects.

Dustin K Bauknight, Victoria Osinski, Siva Sai Krishna Dasa, Anh T Nguyen, Melissa A Marshall, Julia Hartman, Matthew Harms, Gavin O'Mahony, Jeremie Boucher, Alexander L Klibanov and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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

12 authors at 2 institutions in 2 countries.

Dustin K BauknightDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States of America.ORCID 0000-0002-1292-3297
Victoria OsinskiRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United States of America.ORCID 0000-0002-8969-8454
Siva Sai Krishna DasaDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States of America.
Anh T NguyenRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United States of America.
Melissa A MarshallRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United States of America.
Julia HartmanDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States of America.
Matthew HarmsResearch and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Gavin O'MahonyResearch and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0001-5944-1271
Jeremie BoucherResearch and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Alexander L KlibanovDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States of America.
Coleen A McNamaraRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United States of America.
Kimberly A KellyDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States of America.
University of Virginia · USAstraZeneca (Sweden) · SE

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
ROLE OF LIPOXYGENASES IN ATHEROGENESIS IN DIABETES MELLITUSP01HL055798 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HEDRICK, CATHERINE C · 1995 to 2016
$28.4M
Training in Mechanisms of Cardiovascular DiseasesT32HL072742 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI TOBACMAN, LARRY S · 2003 to 2013
$3.7M
Training Program in Cardiac InnovationT32HL144472 · NHLBI · UNIVERSITY OF MINNESOTA · PI Peter A Crawford, SAMUEL C DUDLEY · 2019 to 2026
$2.6M
Highly Specific and Efficient Vectors for Targeting Pancreatic CancerR01CA168712 · NCI · UNIVERSITY OF VIRGINIA · PI FRENCH, BRENT A, KELLY, KIMBERLY A. · 2014 to 2017
$2.0M
Development of Molecularly Targeted Imaging Agents for Early Detection of PDACR01CA137071 · NCI · UNIVERSITY OF VIRGINIA · PI KELLY, KIMBERLY A. · 2008 to 2012
$1.3M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA137071NCI NIH HHS R01 CA168712NHLBI NIH HHS P01 HL055798NHLBI NIH HHS T32 HL072742NHLBI NIH HHS T32 HL144472
6 · The paper itself

Abstract

Targeted nanoparticle delivery is a promising strategy for increasing efficacy and limiting side effects of therapeutics. When designing a targeted liposomal formulation, the in vivo biodistribution of the particles must be characterized to determine the value of the targeting approach. Peroxisome proliferator-activated receptor (PPAR) agonists effectively treat metabolic syndrome by decreasing dyslipidemia and insulin resistance but side effects have limited their use, making them a class of compounds that could benefit from targeted liposomal delivery. The adipose targeting sequence peptide (ATS) could fit this role, as it has been shown to bind to adipose tissue endothelium and induce weight loss when delivered conjugated to a pro-apoptotic peptide. To date, however, a full assessment of ATS in vivo biodistribution has not been reported, leaving important unanswered questions regarding the exact mechanisms whereby ATS targeting enhances therapeutic efficacy. We designed this study to evaluate the biodistribution of ATS-conjugated liposomes loaded with the PPARα/γ dual agonist tesaglitazar in leptin-deficient ob/ob mice. The ATS-liposome biodistribution in adipose tissue and other organs was examined at the cellular and tissue level using microscopy, flow cytometry, and fluorescent molecular tomography. Changes in metabolic parameters and gene expression were measured by target and off-target tissue responses to the treatment. Unexpectedly, ATS targeting did not increase liposomal uptake in adipose relative to other tissues, but did increase uptake in the kidneys. Targeting also did not significantly alter metabolic parameters. Analysis of the liposome cellular distribution in the stromal vascular fraction with flow cytometry revealed high uptake by multiple cell types. Our findings highlight the need for thorough study of in vivo biodistribution when evaluating a targeted therapy.

Indexed as

Drug Delivery SystemsAdipose TissueAlkanesulfonatesAnimalsEndothelial CellsLeukocytesLiposomesMacrophagesMaleMice, Inbred C57BLOrgan SpecificityPeptidesPhenylpropionatesAlkanesulfonatesLiposomesPeptidesPhenylpropionatestesaglitazar

Identifiers

PMID31725756
PMCPMC6855449
OpenAlexW2989057568

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.