Evidence map›Paper›PMID 26211608›Full record

ArticleOsteoarthritis and cartilage2016

Charge based intra-cartilage delivery of single dose dexamethasone using Avidin nano-carriers suppresses cytokine-induced catabolism long term.

A G Bajpayee, M A Quadir, P T Hammond, A J Grodzinsky

Open access · bronzeAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. Pooled it
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  12. Branched poly-l-lysine for cartilage penetrating carriers.Bioengineering & translational medicine · 2024
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  17. The Current Role of Disease-modifying Osteoarthritis Drugs.The archives of bone and joint surgery · 2023
    Review
  18. Review
  19. Article
  20. Article

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

A G BajpayeeDepartment of Mechanical Engineering, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
M A QuadirDepartment of Chemical Engineering and Koch Institute of Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
P T HammondDepartment of Chemical Engineering and Koch Institute of Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
A J GrodzinskyDepartment of Mechanical Engineering, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Biological Engineering, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Electrical Engineering & Computer Science, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: alg@mit.edu.
IIT@MIT · US

Funding

Mucin Glycans in the Regulation of Microbial VirulenceR01EB017755 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI RIBBECK, KATHARINA · 2013 to 2022
$3.6M
Cartilage Repair Using Self Assembling Peptide ScaffoldsR01AR060331 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRODZINSKY, ALAN J. · 2012 to 2016
$1.7M
NIAMS NIH HHS R01 AR060331NIBIB NIH HHS EB017755NIBIB NIH HHS R01 EB017755
6 · The paper itself

Abstract

objectiveAvidin exhibits ideal characteristics for targeted intra-cartilage drug delivery: its small size and optimal positive charge enable rapid penetration through full-thickness cartilage and electrostatic binding interactions that give long half-lives in vivo. Here we conjugated Avidin with dexamethasone (DEX) and tested the hypothesis that single-dose Avidin-delivered DEX can ameliorate catabolic effects in cytokine-challenged cartilage relevant to post-traumatic OA.

methodsAvidin was covalently conjugated with DEX using fast (ester) and slow, pH-sensitive release (hydrazone) linkers. DEX release kinetics from these conjugates was characterized using (3)H-DEX-Avidin (scintillation counting). Cartilage explants treated with IL-1α were cultured with or without Avidin-DEX conjugates and compared to soluble DEX. Sulfated-glycosaminoglycan (sGAG) loss and biosynthesis rates were measured using DMMB assay and (35)S-incorporation, respectively. Chondrocyte viability was measured using fluorescence staining.

resultsEster linker released DEX from Avidin significantly faster than hydrazone under physiological buffer conditions. Single dose Avidin-DEX suppressed cytokine-induced sGAG loss over 3-weeks, rescued IL-1α-induced cell death, and restored sGAG synthesis levels without causing cytotoxicity. The two Avidin-DEX conjugates in 1:1 combination (fast:slow) had the most prominent bioactivity compared to single dose soluble-DEX, which had a shorter-lived effect and thus needed continuous replenishment throughout the culture period to ameliorate catabolic effects.

conclusionIntra-cartilage drug delivery remains inadequate as drugs rapidly clear from the joint, requiring multiple injections or sustained release of high doses in synovial fluid. A single dose of Avidin-conjugated drug enables rapid uptake and sustained delivery inside cartilage at low intratissue doses, and potentially can minimize unwanted drug exposure to other joint tissues.

Indexed as

AvidinDrug CarriersAnimalsCartilage, ArticularCattleCell SurvivalChondrocytesDexamethasoneGlucocorticoidsGlycosaminoglycansInterleukin-1alphaIn Vitro TechniquesMetabolismNanoparticlesAvidinDexamethasoneDrug CarriersGlucocorticoidsGlycosaminoglycansInterleukin-1alphaAvidinCartilage repairCytokineDexamethasoneElectrostatic interactionsIntra-cartilage delivery

Identifiers

PMID26211608
PMCPMC4695287
OpenAlexW1038569680

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.