Evidence map›Paper›PMID 34062883›Full record

ArticlePharmaceutics2021

Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells.

Henry T Hsueh, Yoo-Chun Kim, Ian Pitha, Matthew D Shin, Cynthia A Berlinicke, Renee Ti Chou, Elizabeth Kimball, Julie Schaub, Sarah Quillen, Kirby T Leo and 18 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Next generation therapeutics for retinal neurodegenerative diseases.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Review
  6. Long-Acting Ocular Injectables: Are We Looking In The Right Direction?Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  7. Engineered peptide-drug conjugate provides sustained protection of retinal ganglion cells with topical administration in rats.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. New strategies for neuro protection in glaucoma.Frontiers in cell and developmental biology · 2022
    Review
  13. Article
  14. 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

28 authors at 2 institutions in 1 country.

Henry T HsuehCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Yoo-Chun KimCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Ian PithaCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Matthew D ShinCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Cynthia A BerlinickeDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Renee Ti ChouDepartment of Computational Biology, Bioinformatics, and Genomics, Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.ORCID 0000-0002-8755-6938
Elizabeth KimballDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Julie SchaubDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Sarah QuillenDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Kirby T LeoCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0003-1717-5862
Hyounkoo HanCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Amy XiaoCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Youngwook KimCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Matthew AppellCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Usha RaiCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
HyeYoung KwonCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Patricia KolodziejskiCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Laolu OgunnaikeCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Nicole M AndersThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Avelina HemingwayThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Joan L JefferysDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Abhijit A DateCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0001-6617-882X
Charles EberhartCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Thomas V JohnsonCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Harry A QuigleyCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Donald J ZackCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0002-7966-1973
Justin HanesCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Laura M EnsignCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0002-6949-7911
Johns Hopkins University · USUniversity of Maryland, College Park · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Sustained-release of novel neuroprotective agents for treatment of glaucomaR01EY026578 · NEI · JOHNS HOPKINS UNIVERSITY · PI ENSIGN, LAURA · 2016 to 2020
$2.0M
Acquisition of a triple quadrupole mass spectrometer for small molecule analysisS10OD020091 · OD · JOHNS HOPKINS UNIVERSITY · PI RUDEK, MICHELLE A · 2015 to 2015
$314k
Guerreri Family Research Fund N/AHartwell Foundation Postdoctoral Fellowship N/ANEI NIH HHS P30 EY001765NIH HHS P30CA006973NIH HHS P30EY001765NIH HHS R01EY026578NIH HHS S10OD020091NIH HHS UL1TR003098Research to Prevent Blindness Sybil B. Harrington Special Scholar Award and a departmental grantRobert H. Smith Family Foundation N/A
6 · The paper itself

Abstract

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

Indexed as

glaucomaneuroprotectionocular drug deliverypamoic acidsunitinibtyrosine kinase inhibitor

Identifiers

PMID34062883
PMCPMC8147274
OpenAlexW3159028856

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.