Evidence map›Paper›PMID 40441493›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2025

A novel cationic liposome-formulated toll like receptor (TLR) 7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity.

Fatima A Hamid, Nguyet-Minh Nguyen Le, Daihyun Song, Hardik Amin, Linda Hicks, Sophia Bird, Karthik Siram, Brooke Hoppe, Borries Demeler, Jay T Evans and 2 more

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Solid-Phase Glycolipid Synthesis Expedites Liposome Functionalization.Journal of the American Chemical Society · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Fatima A HamidDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, Seattle, WA, USA; Department of Pharmacology, Medical School, University of Minnesota, Minneapolis, MN, USA.
Nguyet-Minh Nguyen LeDepartment of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA.
Daihyun SongDepartment of Pharmacology, Medical School, University of Minnesota, Minneapolis, MN, USA.
Hardik AminDepartment of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA.
Linda HicksDepartment of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA.
Sophia BirdDepartment of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB, Canada.
Karthik SiramDepartment of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA.
Brooke HoppeDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, Seattle, WA, USA.
Borries DemelerDepartment of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB, Canada; Department of Chemistry and Biochemistry, University of Montana, Missoula, MT, USA.
Jay T EvansDepartment of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA; Inimmune Corporation, Missoula, MT, USA.
David J BurkhartDepartment of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA; Inimmune Corporation, Missoula, MT, USA. Electronic address: david.j.burkhart@inimmune.com.
Marco PravetoniDepartment of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, Seattle, WA, USA; Department of Pharmacology, Medical School, University of Minnesota, Minneapolis, MN, USA. Electronic address: mprave@uw.edu.

Funding

Vaccines for fentanyl and its derivatives: A strategy to reduce illicit use and overdoseUH3DA048386 · NIDA · UNIVERSITY OF WASHINGTON · PI PRAVETONI, MARCO · 2022 to 2024
$11.0M
Development of an UltraScan Meta-Scheduler for HPC Job SubmissionR01GM120600 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Emre H. Brookes, BORRIES DEMELER · 2016 to 2026
$3.6M
Vaccines for fentanyl and its derivatives: A strategy to reduce illicit use and overdoseUG3DA048386 · NIDA · UNIVERSITY OF MINNESOTA · PI PRAVETONI, MARCO · 2019 to 2020
$3.3M
Nanotechnology-based platform for the development of next-generation vaccines against opioid use disorder (OUD)F31DA059235 · NIDA · UNIVERSITY OF MINNESOTA · PI HAMID, FATIMA ALAMIN AWAD ALKAREEM · 2023 to 2024
$71k
NIAID NIH HHS 75N93020C00039NIAID NIH HHS HHSN272201800048CNIDA NIH HHS F31 DA059235NIDA NIH HHS UG3 DA048386NIDA NIH HHS UH3 DA048386NIGMS NIH HHS R01 GM120600
6 · The paper itself

Abstract

The U.S. opioid epidemic is an extraordinary public health crisis that started in 1990 and significantly accelerated in the last decade. Since 2020, over 100,000 fatal drug overdoses have been reported annually, and 75% of those involved fentanyl and its analogs (F/FA). Accelerating the translation of innovative, effective, and safe treatments is needed to augment existing measures to counteract such a crisis. Active immunization against F/FA and other opioids represents a promising therapeutic and prophylactic strategy for opioid use disorder (OUD) and opioid-induced overdose toxicity. Previously we demonstrated that a vaccine against F/FA comprising a fentanyl-based hapten (F) conjugated to the diphtheria cross-reactive material (CRM), admixed with the novel lipidated toll-like receptor 7/8 (TLR7/8) agonist INI-4001 adsorbed on Alhydrogel® (alum) induced high-affinity fentanyl-specific polyclonal antibodies that protected against fentanyl-induced pharmacological effects in mice, rats, and mini-pigs. Here, INI-4001 was formulated into liposomes with different surface charges, and their impact on F-CRM adsorption, INI-4001 adjuvanticity, and vaccine efficacy were explored. Additionally, as the role of innate immunity in mediating the efficacy of addiction vaccines is largely unknown, we tested these formulations on the activation of innate immunity in vitro. Cationic INI-4001 liposomes surpassed other liposomal and aluminum-based formulations of INI-4001 by enhancing the efficacy of fentanyl vaccines and protecting rats against bradycardia and respiratory depression by blocking the distribution of fentanyl to the brain. Fentanyl vaccines adjuvanted with either cationic INI-4001 liposomes or the aqueous INI-4001 adsorbed to alum induced significant surface expression of co-stimulatory molecules and maturation markers in a murine dendritic cell line (JAWS II), while the former was superior in enhancing the macrophages surface expression of CD40, CD86 and inducible nitric oxide synthase (iNOS), indicative of maturation and activation. These results warrant further investigation of liposome-based formulations of TLR7/8 agonists for improving the efficacy of vaccines targeting F/FA and other drug targets of public health interest.

Indexed as

Analgesics, OpioidFentanylToll-Like Receptor 7Toll-Like Receptor 8VaccinesAnimalsCationsFemaleLiposomesMaleMiceMice, Inbred C57BLRatsAnalgesics, OpioidCationsFentanylLiposomesToll-Like Receptor 7Toll-Like Receptor 8VaccinesAdjuvantsAluminumFentanylImidazoquinolineLiposomesOpioidsToll-like receptorVaccines

Identifiers

PMID40441493
PMCPMC12255520

What OpenQuestion holds

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Registered trials

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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.