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ArticleDrug delivery and translational research2026

Combining Leu-enkephalin nanomedicines with enkephalinase inhibitors: a promising painkiller strategy?

Lucas Prades, Hadjer Hazam, Frédéric Gobeaux, Semen Yesylevskyy, Christophe Ramseyer, Luigi Ranieri, Scander Loukil, Catherine Cailleau, Philippe Sitbon, Patrick Couvreur and 1 more

Abstract read
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In one paragraph

Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Lucas PradesInstitut Galien Paris Saclay, UMR CNRS 8612, Université Paris-Saclay, Orsay Cedex, France.
Hadjer HazamMaladies et Hormones du Système Nerveux, INSERM 1195, Le Kremlin Bicêtre, France.
Frédéric GobeauxUniversité Paris-Saclay, CEA Saclay, CNRS, NIMBE, UMR 3685, LIONS, Gif-Sur-Yvette Cedex, France.
Semen YesylevskyyDepartment of Physics of Biological Systems, Institute of Physics of the National Academy of Sciences of Ukraine, Prospect Nauky 46, Kiev, 03028, Ukraine.
Christophe RamseyerLaboratoire Chrono Environnement, UMR CNRS 6249, Université de Bourgogne Franche-Comté, Besançon, Cedex, France.
Luigi RanieriInstitut Galien Paris Saclay, UMR CNRS 8612, Université Paris-Saclay, Orsay Cedex, France.
Scander LoukilInstitut Galien Paris Saclay, UMR CNRS 8612, Université Paris-Saclay, Orsay Cedex, France.
Catherine CailleauInstitut Galien Paris Saclay, UMR CNRS 8612, Université Paris-Saclay, Orsay Cedex, France.
Philippe SitbonMaladies et Hormones du Système Nerveux, INSERM 1195, Le Kremlin Bicêtre, France.
Patrick CouvreurInstitut Galien Paris Saclay, UMR CNRS 8612, Université Paris-Saclay, Orsay Cedex, France. patrick.couvreur@universite-paris-saclay.fr.
Sinda Lepetre-MouelhiInstitut Galien Paris Saclay, UMR CNRS 8612, Université Paris-Saclay, Orsay Cedex, France. sinda.lepetre@universite-paris-saclay.fr.

Funding

Agence Nationale de la Recherche AAPG2021 NANOPAINKILL
6 · The paper itself

Abstract

This study investigates the potential of a novel nanomedicine approach relying on squalene nanoparticles of endogenous enkephalinase inhibitors (EEI) - opiorphin (OPN) and STR-324 - to alleviate pain by potentiating the action of enkephalins in vivo, in a model of acute inflammatory pain. A library of squalene-based EEI prodrugs was synthesized. These prodrugs were unable to self-assemble into nanoparticles, in contrast to the other squalenoylated prodrugs, probably due to their high hydrophilicity. By incorporating either squalenic acid (SQ) or enkephalin-squalene (LENK-SQ) prodrug as adjuvants with strong self-assembling properties, we successfully formulated nanoparticles of STR- or OPN-SQ (EEI-SQ NPs) and performed their physicochemical characterization. The analgesic efficacy of these formulations was evaluated in a carrageenan-induced pain model using the Hargreaves test to assess hyperalgesia. Nevertheless, the intravenous administration of EEI-SQ NPs caused systemic toxicity which was investigated through in vitro incubation assays. It was discovered that EEI-SQ bioconjugates exhibited strong interactions with divalent anions in physiological media, leading to nanoparticles aggregation, which was further confirmed in silico by molecular dynamics simulations. EEI-SQ NPs administered subcutaneously successfully enhanced the anti-hyperalgesic effect of LENK-SQ NPs. However, it was considered as not relevant enough regarding the observed local toxicity.

Indexed as

AnalgesicsEnkephalin, LeucineHyperalgesiaNanomedicineAnimalsNanoparticlesPainSqualeneAnalgesicsEnkephalin, LeucineSqualeneAnalgesiaEnkephalinEnkephalinase inhibitorsNanomedicinesPainSqualene

Identifiers

What Socratic 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 Socratic graph.