Evidence map›Paper›PMID 39879378›Full record

ArticleMolecular pharmaceutics2025

New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.

Rudra Pangeni, Surendra Poudel, Sara M Herz, Grant Berkbigler, Adam S Duerfeldt, M Imad Damaj, Qingguo Xu

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 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. Article
  2. Article
  3. 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.

Rudra PangeniDepartment of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.ORCID 0000-0003-2025-676X
Surendra PoudelDepartment of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.ORCID 0000-0003-2933-1420
Sara M HerzDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Grant BerkbiglerDepartment of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Adam S DuerfeldtDepartment of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.ORCID 0000-0002-3130-9890
M Imad DamajDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Qingguo XuDepartment of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.ORCID 0000-0003-3191-0771

Funding

Sustained release of fenofibrate for the treatment of diabetic retinopathyR01EY033477 · NEI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Jian-Xing Jay Ma, QINGGUO XU · 2022 to 2026
$2.7M
Small Molecule PPAR-alpha Agonism as a Novel Approach to Treat Eye Vascular DiseasesR01EY030472 · NEI · UNIVERSITY OF OKLAHOMA · PI DUERFELDT, ADAM SCOTT · 2020 to 2024
$2.1M
(PQ12) Peroxisome proliferator-activated receptor alpha agonists as potential treatment for chemotherapy-induced peripheral neuropathyR01CA219637 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DAMAJ, M. IMAD, GEWIRTZ, DAVID A. · 2018 to 2021
$1.2M
Hit to Lead Optimization of a Systemically Available Treatment for Diabetic RetinopathyR21EY028279 · NEI · UNIVERSITY OF OKLAHOMA · PI DUERFELDT, ADAM SCOTT · 2017 to 2018
$422k
NCI NIH HHS R01 CA219637NEI NIH HHS R01 EY030472NEI NIH HHS R01 EY033477NEI NIH HHS R21 EY028279
6 · The paper itself

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy. To address these limitations, an optimized oil-in-water (o/w) microemulsion formulation was developed using Box-Behnken design to enhance the solubility and intestinal permeability of A190. The A190 microemulsion exhibited physical stability with a droplet size of approximately 100 nm and a drug loading efficiency of greater than 95%. The effective and apparent permeability of A190 from the microemulsion was significantly higher compared to that of free A190 dispersion, respectively. Additionally, no significant impact on the cell viability was observed, indicating less toxicity and a good biocompatibility of the formulation components. The oral bioavailability of A190 microemulsion was approximately 5-fold higher compared to A190 dispersion, demonstrating the microemulsion's potential to greatly enhance the oral bioavailability of hydrophobic drugs. Furthermore, our findings reveal that orally administered A190 microemulsion effectively reduced CIPN-induced mechanical hypersensitivity, likely mediated through PPARα activation. A190 microemulsion was found to be equally effective at reducing the chronic inflammatory complete Freund's adjuvant-induced pain. These results underscore A190s potential as a nonopioid therapeutic candidate, utilizing a novel microemulsion formulation for the management of chemotherapy-induced neuropathic pain and chronic inflammatory pain.

Indexed as

Antineoplastic AgentsPeripheral Nervous System DiseasesPPAR alphaAdministration, OralAnimalsBiological AvailabilityCell SurvivalEmulsionsHumansMaleMiceRatsRats, Sprague-DawleySolubilityAntineoplastic AgentsEmulsionsPPAR alphachronic inflammatory painnonaddictive analgesicoral bioavailabilityperipheral neuropathypermeabilityperoxisome proliferator-activated receptor

Identifiers

PMID39879378
PMCPMC11881135

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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.