Evidence map›Paper›PMID 25523518›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2015

Tear-mediated delivery of nanoparticles through transcytosis of the lacrimal gland.

Pang-Yu Hsueh, Maria C Edman, Guoyong Sun, Pu Shi, Shi Xu, Yi-An Lin, Honggang Cui, Sarah F Hamm-Alvarez, J Andrew MacKay

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

8 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Protein and polypeptide mediated delivery to the eye.Advanced drug delivery reviews · 2022
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Dry eye disease immune responses and topical therapy.Eye and vision (London, England) · 2019
    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

9 authors at 2 institutions in 1 country.

Pang-Yu HsuehDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Maria C EdmanDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Guoyong SunDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Pu ShiDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Shi XuDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Yi-An LinDepartment of Chemical and Biomolecular Engineering, John Hopkins University, Baltimore, MD 21218, USA.
Honggang CuiDepartment of Chemical and Biomolecular Engineering, John Hopkins University, Baltimore, MD 21218, USA.
Sarah F Hamm-AlvarezDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: jamackay@usc.edu.
University of Southern California · USJohns Hopkins University · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Research Supplements to Promote DiversityR01EY011386 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAMM-ALVAREZ, SARAH F · 1996 to 2025
$9.3M
Ad5 Fiber Entry and Trafficking in Lacrimal AciniR01EY017293 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAMM-ALVAREZ, SARAH F · 2006 to 2010
$2.3M
Intracellular switching using genetically engineered protein microdomainsR01GM114839 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACKAY, JOHN ANDREW · 2015 to 2019
$1.9M
A rapid, reversible switch for controlling intracellular traffickingR21EB012281 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACKAY, JOHN ANDREW · 2010 to 2011
$438k
NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NEI NIH HHS R01EY011386NEI NIH HHS R01 EY017293NEI NIH HHS R01EY017293NEI NIH HHS R01EY017293S1NIBIB NIH HHS R21 EB012281NIBIB NIH HHS R21EB012281NIGMS NIH HHS R01 GM114839
6 · The paper itself

Abstract

Rapid clearance from the tears presents a formidable obstacle to the delivery of peptide drugs to the eye surface. This impedes therapies for ocular infections, wound healing, and dry-eye disease that affect the vision of millions worldwide. To overcome this challenge, this manuscript explores a novel strategy to reach the ocular surface via receptor-mediated transcytosis across the lacrimal gland (LG), which produces the bulk of human tears. The LG abundantly expresses the coxsackievirus and adenovirus receptor (CAR); furthermore, we recently reported a peptide-based nanoparticle (KSI) that targets CAR on liver cells. This manuscript reports the unexpected finding that KSI both targets and transcytoses into the LG acinar lumen, which drains to tear ducts. When followed using ex vivo live cell imaging KSI rapidly accumulates in lumen formed by LG acinar cells. LG transduction with a myosin Vb tail, which is dominant negative towards transcytosis, inhibits lumenal accumulation. Transcytosis of KSI was confirmed in vivo by confocal and TEM imaging of LG tissue following administration of KSI nanoparticles. These findings suggest that it is possible to target nanomaterials to the tears by targeting certain receptors on the LG. This design strategy represents a new opportunity to overcome barriers to ocular delivery.

Indexed as

Acinar CellsAnimalsCoxsackie and Adenovirus Receptor-Like Membrane ProteinDry Eye SyndromesEndocytosisFemaleHepatocytesLacrimal ApparatusMiceMice, Inbred BALB CNanoparticlesPeptidesPolymersPrimary Cell CultureRabbitsTearsCoxsackie and Adenovirus Receptor-Like Membrane ProteinPeptidesPolymersCoxsackievirus and adenovirus receptorElastin-like polypeptideKnobLacrimal glandTranscytosis

Identifiers

PMID25523518
PMCPMC4456098
OpenAlexW2084072716

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.