Evidence map›Paper›PMID 28063892›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2017

An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration.

Lei Zhao, Guojun Chen, Jun Li, Yingmei Fu, Timur A Mavlyutov, Annie Yao, Robert W Nickells, Shaoqin Gong, Lian-Wang Guo

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Chemical Approaches to Synthetic Drug Delivery Systems for Systemic Applications.Angewandte Chemie (International ed. in English) · 2022
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Sigma 1 Receptor Modulates Optic Nerve Head Astrocyte Reactivity.Investigative ophthalmology & visual science · 2021
    Article
  16. Article
  17. Review
  18. Pranoprofen Nanoparticles WithFrontiers in bioengineering and biotechnology · 2020
    Article
  19. Review
  20. Sigma 1 receptor: A novel therapeutic target in retinal disease.Progress in retinal and eye research · 2018
    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

9 authors at 4 institutions in 2 countries.

Lei ZhaoDepartment of Surgery, 5151 Wisconsin Institute for Medical Research, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA.
Guojun ChenDepartment of Materials Science and Engineering, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
Jun LiDepartment of Surgery, 5151 Wisconsin Institute for Medical Research, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA; Department of Ophthalmology, The First Hospital of China Medical University, Shenyang 110001, China.; Department of Ophthalmology, The 3rd People's Hospital of Dalian, Dalian 116033, China.
Yingmei FuDepartment of Surgery, 5151 Wisconsin Institute for Medical Research, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wanping Nan Road, Shanghai 200030, China.
Timur A MavlyutovDepartment of Surgery, 5151 Wisconsin Institute for Medical Research, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA.
Annie YaoDepartment of Surgery, 5151 Wisconsin Institute for Medical Research, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA.
Robert W NickellsDepartment of Ophthalmology and Vision Sciences, University of Wisconsin-Madison, 1300 University Ave, Madison, WI 53706, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI 53705, USA.
Shaoqin GongDepartment of Materials Science and Engineering, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53715, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: shaoqingong@wisc.edu.
Lian-Wang GuoDepartment of Surgery, 5151 Wisconsin Institute for Medical Research, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: guo@surgery.wisc.edu.
University of Wisconsin–Madison · USSmith-Kettlewell Eye Research Institute · USShanghai Mental Health Center · CNThe Third People's Hospital of Dalian City · CN

Funding

UW Vision Research Core - Administrative CoreP30EY016665 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI ROBERT W NICKELLS · 2005 to 2026
$12.6M
The molecular mechanism of retinal ganglion cell deathR01EY012223 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI NICKELLS, ROBERT W · 2005 to 2017
$6.3M
Development of unimolecular nanoparticle-mediated periadventitial drug delivery system for sustained and targeted inhibition of intimal hyperplasia following open vascular reconstructionR01HL129785 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GONG, SHAOQIN -, GUO, LIANWANG · 2016 to 2019
$2.0M
Sigma-1 Chaperone-Mediated in vivo Neuroprotection in the RetinaR01EY022678 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG · 2012 to 2016
$1.7M
Targeted Therapy of Neuroendocrine Cancers Via the Notch Signaling PathwayK25CA166178 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI GONG, SHAOQIN - · 2013 to 2017
$994k
NCI NIH HHS K25 CA166178NEI NIH HHS P30 EY016665NEI NIH HHS R01 EY012223NEI NIH HHS R01 EY022678NHLBI NIH HHS R01 HL129785
6 · The paper itself

Abstract

Glaucoma is a common blinding disease characterized by loss of retinal ganglion cells (RGCs). To date, there is no clinically available treatment directly targeting RGCs. We aim to develop an RGC-targeted intraocular drug delivery system using unimolecular micelle nanoparticles (unimNPs) to prevent RGC loss. The unimNPs were formed by single/individual multi-arm star amphiphilic block copolymer poly(amidoamine)-polyvalerolactone-poly(ethylene glycol) (PAMAM-PVL-PEG). While the hydrophobic PAMAM-PVL core can encapsulate hydrophobic drugs, the hydrophilic PEG shell provides excellent water dispersity. We conjugated unimNPs with the cholera toxin B domain (CTB) for RGC-targeting and with Cy5.5 for unimNP-tracing. To exploit RGC-protective sigma-1 receptor (S1R), we loaded unimNPs with an endogenous S1R agonist dehydroepiandrosterone (DHEA) as an FDA-approved model drug. These unimNPs produced a steady DHEA release in vitro for over two months at pH7.4. We then co-injected (mice, intraocular) unimNPs with the glutamate analog N-methyl-d-aspartate (NMDA), which is excito-toxic and induces RGC death. The CTB-conjugated unimNPs (i.e., targeted NPs) accumulated at the RGC layer and effectively preserved RGCs at least for 14days, whereas the unimNPs without CTB (i.e., non-targeted NPs) showed neither accumulation at nor protection of NMDA-treated RGCs. Consistent with S1R functions, targeted NPs relative to non-targeted NPs showed markedly better inhibitory effects on apoptosis and oxidative/inflammatory stresses in the RGC layer. Hence, the DHEA-loaded, CTB-conjugated unimNPs represent an RGC/S1R dual-targeted nanoplatform that generates an efficacious template for further development of a sustainable intraocular drug delivery system to protect RGCs, which may be applicable to treatments directed at glaucomatous pathology.

Indexed as

MicellesAnimalsApoptosisCholera ToxinDehydroepiandrosteroneDendrimersDrug Delivery SystemsHydrophobic and Hydrophilic InteractionsIntravitreal InjectionsMiceMice, Inbred C57BLNanoparticlesPolyethylene GlycolsReceptors, sigmaRetinal Ganglion CellsSigma-1 ReceptorCholera ToxinDehydroepiandrosteroneDendrimersMicellesPEG-PAMAMPolyethylene GlycolsReceptors, sigmaSigma-1 ReceptorCholera toxin B domainExcitotoxicityGanglion cell targetingRetinaSigma-1 receptorTargeted drug deliveryUnimolecular micelles

Identifiers

PMID28063892
PMCPMC5323250
OpenAlexW2571369470

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.