Evidence map›Paper›PMID 34653564›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2021

Thermoresponsive polymeric dexamethasone prodrug for arthritis pain.

Gang Zhao, Rongguo Ren, Xin Wei, Zhenshan Jia, Ningrong Chen, Yuanyuan Sun, Zhifeng Zhao, Subodh M Lele, Haizhen A Zhong, Mary B Goldring and 2 more

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 47 citations in OpenAlex.

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  8. Advances in the use of nanotechnology for treating gout.Nanomedicine (London, England) · 2025
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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 4 institutions in 1 country.

Gang ZhaoDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA.
Rongguo RenDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Xin WeiDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Zhenshan JiaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ningrong ChenDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Yuanyuan SunDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Zhifeng ZhaoDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Subodh M LeleDepartment of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900, USA.
Haizhen A ZhongDepartment of Chemistry, University of Nebraska at Omaha, Omaha, NE 68182, USA.
Mary B GoldringHospital for Special Surgery, New York, NY 10021, USA.
Steven R GoldringEnsign Pharmaceutical, Inc., Omaha, NE 68106, USA; Hospital for Special Surgery, New York, NY 10021, USA.
Dong WangDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; Ensign Pharmaceutical, Inc., Omaha, NE 68106, USA; Department of Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: dwang@unmc.edu.
University of Nebraska Medical Center · USHospital for Special Surgery · USNebraska Medical Center · USUniversity of Nebraska at Omaha · US

Funding

ProGel Technology for Better Management of Osteoarthritis PainR44DA051278 · NIDA · ENSIGN PHARMACEUTICAL, INC · PI GOLDRING, STEVEN · 2020 to 2022
$1.9M
Nanomedicine Development for Systemic Lupus ErythematosusR01AI119090 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI WANG, DONG · 2016 to 2020
$1.9M
NIAID NIH HHS R01 AI119090NIDA NIH HHS R44 DA051278
6 · The paper itself

Abstract

Intra-articular (IA) glucocorticoids (GC) are commonly used for clinical management of both osteoarthritis and rheumatoid arthritis, but their efficacy is limited by the relatively short duration of action and associated side effects. To provide sustained efficacy and to improve the safety of GCs, we previously developed a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based dexamethasone (Dex) prodrug. Serendipitously, we discovered that, by increasing the Dex content of the prodrug to unusually high levels, the aqueous solution of the polymeric prodrug becomes thermoresponsive, transitioning from a free-flowing liquid at 4 °C to a hydrogel at 30 °C or greater. Upon IA injection, the prodrug solution forms a hydrogel (ProGel-Dex) that is retained in the joint for more than 1 month, where it undergoes gradual dissolution, releasing the water-soluble polymeric prodrug. The released prodrug is swiftly internalized and intracellularly processed by phagocytic synoviocytes to release free Dex, resulting in sustained amelioration of joint inflammation and pain in rodent models of inflammatory arthritis and osteoarthritis. The low molecular weight (6.8 kDa) of the ProGel-Dex ensures rapid renal clearance once it escapes the joint, limiting systemic GC exposure and risk of potential off-target side effects. The present study illustrates the translational potential of ProGel-Dex as a potent opioid-sparing, locally delivered adjuvant analgesic for sustained clinical management of arthritis pain and inflammation. Importantly, the observed thermoresponsive properties of the prodrug establishes ProGel as a platform technology for the local delivery of a broad spectrum of therapeutic agents to treat a diverse array of pathological conditions.

Indexed as

Arthritis, ExperimentalArthritis, RheumatoidProdrugsAnimalsDexamethasonePainDexamethasoneProdrugsArthritisGlucocorticoidHydrogelPainPolymeric prodrugThermoresponsive

Identifiers

PMID34653564
PMCPMC8599655
OpenAlexW3206194663

What Socratic 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 Socratic graph.