Evidence map›Paper›PMID 34417826›Full record

ArticleInflammatory bowel diseases2022

Oral Delivery of Encapsulated All-Trans Retinoic Acid Ameliorates Disease in Rodent Models of Colitis.

Ferdinando Nicoletti, Laura Hammer, Stacia Furtado, Katia Mangano, Edith Mathiowitz, Benjamin Green, Dominick L Auci

Open access · greenAbstract read
In one paragraph

Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. 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

7 authors at 3 institutions in 2 countries.

Ferdinando NicolettiUniversity of Catania, Catania, Italy.
Laura HammerTherapyx, Inc., Louisville, Kentucky, USA.
Stacia FurtadoBrown University, Providence Rhode Island, USA.
Katia ManganoUniversity of Catania, Catania, Italy.
Edith MathiowitzBrown University, Providence Rhode Island, USA.
Benjamin GreenTherapyx, Inc., Louisville, Kentucky, USA.
Dominick L AuciTherapyx, Inc., Louisville, Kentucky, USA.ORCID 0000-0001-5315-9873
Therapyx (United States) · USBrown University · USUniversity of Catania · IT

Funding

Delivery of Nanoencapsulated TGFbeta and ATRA for the Treatment of IBDR44AI080009 · NIAID · THERAPYX, INC. · PI AUCI, DOMINICK · 2011 to 2019
$6.0M
NIAID NIH HHS R44 AI080009
6 · The paper itself

Abstract

backgroundAll-trans retinoic acid (ATRA) is a biologically active isomer of retinoic acid (RA). Topical ATRA (retin-a, retin-a micro, atralin, renova, and avita) is the active pharmaceutical ingredient for FDA-approved treatments for acne and skin wrinkles. Oral formulations (Vesanoid) treat acute promyelocytic leukemia, but oral dosing can induce severe side effects. Despite benefits in various rodent models of inflammatory bowel disease (IBD), toxicity and controversial clinical observations have diminished enthusiasm for ATRA IBD clinical trials. To circumvent these issues and to use ATRA's key role in maintaining gut tolerance, we developed a poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) encapsulated ATRA formulation aimed at directing ATRA delivery to immune structures of the gut, limiting systemic exposure. Initially, ATRA MS was developed as a component of a combinatorial product (TreXTAM) that also contained encapsulated transforming growth factor (TGF)-β and ATRA in a 1:2 w/w ratio. Although the combination was optimal, benefit was also observed when ATRA MS was given alone in the CD4+ CD25-T-cell adoptive transfer (ACT) colitis model.

methodsWe used the ACT and DSS-induced murine models of colitis to expand on the dose-dependent effects of oral ATRA MS when given alone. The DSS model was also used to compare the efficacy of ATRA MS and soluble ATRA, while healthy animals were used to compare the pharmacokinetics of the two drugs.

resultsIn both the ACT and DSS-induced murine models of colitis, ATRA MS was observed to be effective in ameliorating disease. ATRA MS was also observed to be more effective than soluble ATRA in these models and displayed more favorable pharmacokinetics.

conclusionsWe suggest ATRA MS, as a standalone product, may attenuate IBD and perhaps limit fibrosis, while limiting systemic side effects.

Indexed as

ColitisInflammatory Bowel DiseasesAnimalsMiceRodentiaTransforming Growth Factor betaTretinoinTransforming Growth Factor betaTretinoinATRAIBDOral

Identifiers

PMID34417826
PMCPMC8889276
OpenAlexW3193946477

What OpenQuestion holds

Textmetadata
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.